{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,12]],"date-time":"2026-03-12T06:44:28Z","timestamp":1773297868223,"version":"3.50.1"},"reference-count":70,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2018,7,5]],"date-time":"2018-07-05T00:00:00Z","timestamp":1530748800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2018,7,5]],"date-time":"2018-07-05T00:00:00Z","timestamp":1530748800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"name":"The Lambert Initiative for Cannabinoid Therapeutics"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sci Rep"],"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Recent surveys suggest that many parents are using illicit cannabis extracts in the hope of managing seizures in their children with epilepsy. In the current Australian study we conducted semi-structured interviews with families of children with diverse forms of epilepsy to explore their attitudes towards and experiences with using cannabis extracts. This included current or previous users of cannabis extracts to treat their child\u2019s seizures (n\u2009=\u200941 families), and families who had never used (n\u2009=\u200924 families). For those using cannabis, extracts were analysed for cannabinoid content, with specific comparison of samples rated by families as \u201ceffective\u201d versus those rated \u201cineffective\u201d. Results showed that children given cannabis extracts tended to have more severe epilepsy historically and had trialled more anticonvulsants than those who had never received cannabis extracts. There was high variability in the cannabinoid content and profile of cannabis extracts rated as \u201ceffective\u201d, with no clear differences between extracts perceived as \u201ceffective\u201d and \u201cineffective\u201d. Contrary to family\u2019s expectations, most samples contained low concentrations of cannabidiol, while \u0394<jats:sup>9<\/jats:sup>-tetrahydrocannabinol was present in nearly every sample. These findings highlight profound variation in the illicit cannabis extracts being currently used in Australia and warrant further investigations into the therapeutic\u00a0value of cannabinoids in epilepsy.<\/jats:p>","DOI":"10.1038\/s41598-018-28127-0","type":"journal-article","created":{"date-parts":[[2018,6,29]],"date-time":"2018-06-29T09:46:50Z","timestamp":1530265610000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":42,"title":["Composition and Use of Cannabis Extracts for Childhood Epilepsy in the Australian Community"],"prefix":"10.1038","volume":"8","author":[{"given":"A.","family":"Suraev","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"N.","family":"Lintzeris","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"J.","family":"Stuart","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"R. C.","family":"Kevin","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"R.","family":"Blackburn","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"E.","family":"Richards","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"J. C.","family":"Arnold","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"C.","family":"Ireland","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"L.","family":"Todd","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"D. J.","family":"Allsop","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"I. S.","family":"McGregor","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2018,7,5]]},"reference":[{"key":"28127_CR1","doi-asserted-by":"publisher","first-page":"304","DOI":"10.1016\/S1474-4422(15)00250-1","volume":"15","author":"A McTague","year":"2016","unstructured":"McTague, A., Howell, K. B., Cross, J. H., Kurian, M. A. & Scheffer, I. E. The genetic landscape of the epileptic encephalopathies of infancy and childhood. Lancet Neurol. 15, 304\u2013316 (2016).","journal-title":"Lancet Neurol."},{"key":"28127_CR2","doi-asserted-by":"publisher","first-page":"1069","DOI":"10.1111\/j.1528-1167.2009.02397.x","volume":"51","author":"P Kwan","year":"2010","unstructured":"Kwan, P. et al. Definition of drug resistant epilepsy: consensus proposal by the ad hoc Task Force of the ILAE Commission on Therapeutic Strategies. Epilepsia 51, 1069\u20131077 (2010).","journal-title":"Epilepsia"},{"key":"28127_CR3","doi-asserted-by":"publisher","first-page":"1548","DOI":"10.1212\/WNL.0b013e3182563b19","volume":"78","author":"M Brodie","year":"2012","unstructured":"Brodie, M., Barry, S., Bamagous, G., Norrie, J. & Kwan, P. Patterns of treatment response in newly diagnosed epilepsy. Neurology 78, 1548\u20131554 (2012).","journal-title":"Neurology"},{"key":"28127_CR4","doi-asserted-by":"publisher","first-page":"279","DOI":"10.1001\/jamaneurol.2017.3949","volume":"75","author":"Z Chen","year":"2018","unstructured":"Chen, Z., Brodie, M. J., Liew, D. & Kwan, P. Treatment outcomes in patients with newly diagnosed epilepsy treated with established and new antiepileptic drugs: a 30-year longitudinal cohort study. JAMA Neurol 75, 279\u2013286 (2018).","journal-title":"JAMA Neurol"},{"key":"28127_CR5","doi-asserted-by":"publisher","first-page":"369","DOI":"10.1016\/j.seizure.2011.01.004","volume":"20","author":"MJ Brodie","year":"2011","unstructured":"Brodie, M. J. & Sills, G. J. Combining antiepileptic drugs\u2014rational polytherapy? Seizure 20, 369\u2013375 (2011).","journal-title":"Seizure"},{"key":"28127_CR6","doi-asserted-by":"publisher","first-page":"1294","DOI":"10.1111\/epi.13435","volume":"57","author":"JM Finamore","year":"2016","unstructured":"Finamore, J. M. et al. Seizure outcome after switching antiepileptic drugs: A matched, prospective study. Epilepsia 57, 1294\u20131300 (2016).","journal-title":"Epilepsia"},{"key":"28127_CR7","doi-asserted-by":"publisher","first-page":"77","DOI":"10.1053\/seiz.2002.0593","volume":"11","author":"P Kwan","year":"2002","unstructured":"Kwan, P. & Brodie, M. J. Refractory epilepsy: a progressive, intractable but preventable condition? Seizure 11, 77\u201384 (2002).","journal-title":"Seizure"},{"key":"28127_CR8","doi-asserted-by":"publisher","first-page":"812","DOI":"10.1111\/epi.13342","volume":"57","author":"AE Warren","year":"2016","unstructured":"Warren, A. E., Abbott, D. F., Vaughan, D. N., Jackson, G. D. & Archer, J. S. Abnormal cognitive network interactions in Lennox\u2010Gastaut syndrome: A potential mechanism of epileptic encephalopathy. Epilepsia 57, 812\u2013822 (2016).","journal-title":"Epilepsia"},{"key":"28127_CR9","doi-asserted-by":"publisher","first-page":"307","DOI":"10.1016\/j.yebeh.2014.09.011","volume":"41","author":"SJ Wilson","year":"2014","unstructured":"Wilson, S. J. & Baxendale, S. The new approach to classification: rethinking cognition and behavior in epilepsy. Epilepsy Behav 41, 307\u2013310 (2014).","journal-title":"Epilepsy Behav"},{"key":"28127_CR10","doi-asserted-by":"publisher","first-page":"138","DOI":"10.1016\/j.yebeh.2015.04.009","volume":"47","author":"SA Hussain","year":"2015","unstructured":"Hussain, S. A. et al. Perceived efficacy of cannabidiol-enriched cannabis extracts for treatment of pediatric epilepsy: a potential role for infantile spasms and Lennox\u2013Gastaut syndrome. Epilepsy Behav 47, 138\u2013141 (2015).","journal-title":"Epilepsy Behav"},{"key":"28127_CR11","doi-asserted-by":"publisher","first-page":"574","DOI":"10.1016\/j.yebeh.2013.08.037","volume":"29","author":"BE Porter","year":"2013","unstructured":"Porter, B. E. & Jacobson, C. Report of a parent survey of cannabidiol-enriched cannabis use in pediatric treatment-resistant epilepsy. Epilepsy Behav 29, 574\u2013577 (2013).","journal-title":"Epilepsy Behav"},{"key":"28127_CR12","doi-asserted-by":"publisher","first-page":"49","DOI":"10.1016\/j.yebeh.2015.02.043","volume":"45","author":"CA Press","year":"2015","unstructured":"Press, C. A., Knupp, K. G. & Chapman, K. E. Parental reporting of response to oral cannabis extracts for treatment of refractory epilepsy. Epilepsy Behav 45, 49\u201352 (2015).","journal-title":"Epilepsy Behav"},{"key":"28127_CR13","doi-asserted-by":"publisher","first-page":"334","DOI":"10.1016\/j.yebeh.2017.02.005","volume":"70","author":"AS Suraev","year":"2017","unstructured":"Suraev, A. S. et al. An Australian nationwide survey on medicinal cannabis use for epilepsy: History of antiepileptic drug treatment predicts medicinal cannabis use. Epilepsy Behav 70, 334\u2013340 (2017).","journal-title":"Epilepsy Behav"},{"key":"28127_CR14","unstructured":"Young, S. Marijuana stops child\u2019s severe seizures, http:\/\/edition.cnn.com\/2013\/08\/07\/health\/charlotte-child-medical-marijuana\/index.html (2013)."},{"key":"28127_CR15","unstructured":"D., B. Medical marijuana the key to little Katelyn Lambert\u2019s survival: She suffers up to 1400 seizures a day. https:\/\/www.dailytelegraph.com.au\/newslocal\/central-coast\/medical-marijuana-the-key-to-little-katelyn-lamberts-survival-she-suffers-up-to-1400-seizures-a-day\/news-story\/c9f0464dd5aea508aa2ed1254a46d8f3 (2014)."},{"key":"28127_CR16","doi-asserted-by":"publisher","first-page":"1629","DOI":"10.1111\/j.1476-5381.2012.02207.x","volume":"167","author":"A Hill","year":"2012","unstructured":"Hill, A. et al. Cannabidivarin is anticonvulsant in mouse and rat. Br. J. Pharmacol. 167, 1629\u20131642 (2012).","journal-title":"Br. J. Pharmacol."},{"key":"28127_CR17","doi-asserted-by":"publisher","first-page":"1522","DOI":"10.1111\/j.1528-1167.2010.02523.x","volume":"51","author":"AJ Hill","year":"2010","unstructured":"Hill, A. J. et al. \u03949\u2010Tetrahydrocannabivarin suppresses in vitro epileptiform and in vivo seizure activity in adult rats. Epilepsia 51, 1522\u20131532 (2010).","journal-title":"Epilepsia"},{"key":"28127_CR18","doi-asserted-by":"publisher","first-page":"1131","DOI":"10.1021\/cn5000524","volume":"5","author":"FA Iannotti","year":"2014","unstructured":"Iannotti, F. A. et al. Nonpsychotropic plant cannabinoids, cannabidivarin (CBDV) and cannabidiol (CBD), activate and desensitize transient receptor potential vanilloid 1 (TRPV1) channels in vitro: potential for the treatment of neuronal hyperexcitability. ACS Chem. Neurosci. 5, 1131\u20131141 (2014).","journal-title":"ACS Chem. Neurosci."},{"key":"28127_CR19","unstructured":"Stott, C., Jones, N., Williams, R. & Whalley, B. Use of cannabinoids in the treatment of epilepsy (2017)."},{"key":"28127_CR20","doi-asserted-by":"crossref","unstructured":"Katona, I. In Endocannabinoids Vol. 231, 285\u2013316 (Springer, 2015).","DOI":"10.1007\/978-3-319-20825-1_10"},{"key":"28127_CR21","doi-asserted-by":"publisher","first-page":"264","DOI":"10.1038\/nrn3937","volume":"16","author":"I Soltesz","year":"2015","unstructured":"Soltesz, I. et al. Weeding out bad waves: towards selective cannabinoid circuit control in epilepsy. Nat. Rev. Neurosci. 16, 264\u2013277 (2015).","journal-title":"Nat. Rev. Neurosci."},{"key":"28127_CR22","doi-asserted-by":"publisher","first-page":"2011","DOI":"10.1056\/NEJMoa1611618","volume":"376","author":"O Devinsky","year":"2017","unstructured":"Devinsky, O. et al. Trial of cannabidiol for drug-resistant seizures in the dravet syndrome. N Engl J Med 376, 2011\u20132020 (2017).","journal-title":"N Engl J Med"},{"key":"28127_CR23","unstructured":"Thiele, E. A. et al. Cannabidiol in patients with seizures associated with Lennox-Gastaut syndrome (GWPCARE4): a randomised, double-blind, placebo-controlled phase 3 trial. Lancet (2018)."},{"key":"28127_CR24","doi-asserted-by":"publisher","first-page":"270","DOI":"10.1016\/S1474-4422(15)00379-8","volume":"15","author":"O Devinsky","year":"2016","unstructured":"Devinsky, O. et al. Cannabidiol in patients with treatment-resistant epilepsy: an open-label interventional trial. Lancet Neurol. 15, 270\u2013278 (2016).","journal-title":"Lancet Neurol."},{"key":"28127_CR25","doi-asserted-by":"publisher","first-page":"41","DOI":"10.1016\/j.seizure.2016.01.004","volume":"35","author":"M Tzadok","year":"2016","unstructured":"Tzadok, M. et al. CBD-enriched medical cannabis for intractable pediatric epilepsy: The current Israeli experience. Seizure 35, 41\u201344 (2016).","journal-title":"Seizure"},{"key":"28127_CR26","unstructured":"Gedde, M. & Maa, E. In American Epilepsy Society, 67th Annual Meeting (2013)."},{"key":"28127_CR27","unstructured":"Pellicia, A., Grassi, G., Romano, A. & Crocchialo, P. In Congress on Cannabis and the Cannabinoids, Leiden, The Netherlands: International Association for Cannabis as Medicine. 14."},{"key":"28127_CR28","unstructured":"Davis, J. P. & Ramsey, H. H. In Fed. Proc Vol. 8, 284\u2013285 (1949)."},{"key":"28127_CR29","first-page":"40","volume":"25","author":"R Lorenz","year":"2004","unstructured":"Lorenz, R. On the application of cannabis in paediatrics and epileptology. Neuro Endocrinol Lett 25, 40\u201344 (2004).","journal-title":"Neuro Endocrinol Lett"},{"key":"28127_CR30","doi-asserted-by":"publisher","first-page":"783","DOI":"10.1111\/epi.12610","volume":"55","author":"E Maa","year":"2014","unstructured":"Maa, E. & Figi, P. The case for medical marijuana in epilepsy. Epilepsia 55, 783\u2013786 (2014).","journal-title":"Epilepsia"},{"key":"28127_CR31","doi-asserted-by":"publisher","first-page":"328","DOI":"10.1016\/j.yebeh.2016.12.032","volume":"70","author":"D Sulak","year":"2017","unstructured":"Sulak, D., Saneto, R. & Goldstein, B. The current status of artisanal cannabis for the treatment of epilepsy in the United States. Epilepsy Behav 70, 328\u2013333 (2017).","journal-title":"Epilepsy Behav"},{"key":"28127_CR32","doi-asserted-by":"publisher","first-page":"1246","DOI":"10.1111\/epi.13060","volume":"56","author":"AL Geffrey","year":"2015","unstructured":"Geffrey, A. L., Pollack, S. F., Bruno, P. L. & Thiele, E. A. Drug\u2013drug interaction between clobazam and cannabidiol in children with refractory epilepsy. Epilepsia 56, 1246\u20131251 (2015).","journal-title":"Epilepsia"},{"key":"28127_CR33","doi-asserted-by":"publisher","first-page":"1586","DOI":"10.1111\/epi.13852","volume":"58","author":"TE Gaston","year":"2017","unstructured":"Gaston, T. E. et al. Interactions between cannabidiol and commonly used antiepileptic drugs. Epilepsia 58, 1586\u20131592 (2017).","journal-title":"Epilepsia"},{"key":"28127_CR34","doi-asserted-by":"publisher","first-page":"51","DOI":"10.1080\/14740338.2017.1397128","volume":"17","author":"C Rong","year":"2018","unstructured":"Rong, C. et al. Drug-drug interactions as a result of co-administering \u03949-THC and CBD with other psychotropic agents. Expert Opin Drug Saf. 17, 51\u201354 (2018).","journal-title":"Expert Opin Drug Saf."},{"key":"28127_CR35","doi-asserted-by":"publisher","first-page":"e70052","DOI":"10.1371\/journal.pone.0070052","volume":"8","author":"W Swift","year":"2013","unstructured":"Swift, W., Wong, A., Li, K. M., Arnold, J. C. & McGregor, I. S. Analysis of cannabis seizures in NSW, Australia: cannabis potency and cannabinoid profile. PloS One 8, e70052 (2013).","journal-title":"PloS One"},{"key":"28127_CR36","doi-asserted-by":"publisher","first-page":"679","DOI":"10.1111\/bph.12321","volume":"170","author":"T Hill","year":"2013","unstructured":"Hill, T. et al. Cannabidivarin\u2010rich cannabis extracts are anticonvulsant in mouse and rat via a CB1 receptor\u2010independent mechanism. Br. J. Pharmacol. 170, 679\u2013692 (2013).","journal-title":"Br. J. Pharmacol."},{"key":"28127_CR37","doi-asserted-by":"publisher","first-page":"26","DOI":"10.1016\/j.yebeh.2015.12.040","volume":"56","author":"CC de Oliveira","year":"2016","unstructured":"de Oliveira, C. C. et al. Anticonvulsant activity of \u03b2-caryophyllene against pentylenetetrazol-induced seizures. Epilepsy Behav 56, 26\u201331 (2016).","journal-title":"Epilepsy Behav"},{"key":"28127_CR38","doi-asserted-by":"publisher","first-page":"573","DOI":"10.1016\/0091-3057(82)90418-X","volume":"16","author":"BK Colasanti","year":"1982","unstructured":"Colasanti, B. K., Lindamood, C. & Craig, C. R. Effects of marihuana cannabinoids on seizure activity in cobalt-epileptic rats. Pharmacol. Biochem. Behav. 16, 573\u2013578 (1982).","journal-title":"Pharmacol. Biochem. Behav."},{"key":"28127_CR39","doi-asserted-by":"publisher","first-page":"471","DOI":"10.1016\/0014-4886(73)90088-5","volume":"40","author":"ME Corcoran","year":"1973","unstructured":"Corcoran, M. E., McCaughran, J. A. & Wada, J. A. Acute antiepileptic effects of \u0394 9-tetrahydrocannabinol in rats with kindled seizures. Exp. Neurol 40, 471\u2013483 (1973).","journal-title":"Exp. Neurol"},{"key":"28127_CR40","doi-asserted-by":"publisher","first-page":"95","DOI":"10.1007\/BF00413961","volume":"28","author":"I Izquierdo","year":"1973","unstructured":"Izquierdo, I., Orsingher, O. A. & Berardi, A. C. Effect of cannabidiol and of other cannabis sativa compounds on hippocampal seizure discharges. Psychopharmacologia. 28, 95\u2013102 (1973).","journal-title":"Psychopharmacologia."},{"key":"28127_CR41","doi-asserted-by":"publisher","first-page":"365","DOI":"10.1111\/j.1528-1157.1979.tb04816.x","volume":"20","author":"P Chiu","year":"1979","unstructured":"Chiu, P., Olsen, D. M., Borys, H. K., Karler, R. & Turkanis, S. A. The influence of cannabidiol and \u03b49\u2010tetrahydrocannabinol on cobalt epilepsy in rats. Epilepsia 20, 365\u2013375 (1979).","journal-title":"Epilepsia"},{"key":"28127_CR42","doi-asserted-by":"publisher","first-page":"441","DOI":"10.1016\/0028-3908(86)90240-6","volume":"25","author":"R Karler","year":"1986","unstructured":"Karler, R., Calder, L. & Turkanis, S. Prolonged CNS hyperexcitability in mice after a single exposure to delta-9-tetrahydrocannabinol. Neuropharmacology 25, 441\u2013446 (1986).","journal-title":"Neuropharmacology"},{"key":"28127_CR43","doi-asserted-by":"publisher","first-page":"479","DOI":"10.1111\/j.1476-5381.1980.tb14562.x","volume":"68","author":"R Karler","year":"1980","unstructured":"Karler, R. & Turkanis, S. A. Subacute cannabinoid treatment: anticonvulsant activity and withdrawal excitability in mice. Br. J. Pharmacol. 68, 479\u2013484 (1980).","journal-title":"Br. J. Pharmacol."},{"key":"28127_CR44","doi-asserted-by":"publisher","first-page":"377","DOI":"10.1016\/j.jbi.2008.08.010","volume":"42","author":"PA Harris","year":"2009","unstructured":"Harris, P. A. et al. Research electronic data capture (REDCap) \u2013 A metadata-driven methodology and workflow process for providing translational research informatics support. J Biomed Inform 42, 377\u2013381 (2009).","journal-title":"J Biomed Inform"},{"key":"28127_CR45","doi-asserted-by":"crossref","unstructured":"Guy, W. ECDEU Assessment Manual forPsychopharmacology. US Department of Health and Welfare, 534\u2013537 (1976).","DOI":"10.1037\/e591322011-001"},{"key":"28127_CR46","doi-asserted-by":"publisher","first-page":"351","DOI":"10.1136\/adc.2003.048645","volume":"90","author":"E Bunge","year":"2005","unstructured":"Bunge, E. et al. Reliability and validity of health status measurement by the TAPQOL. Arch Dis Child 90, 351\u2013358 (2005).","journal-title":"Arch Dis Child"},{"key":"28127_CR47","doi-asserted-by":"publisher","first-page":"961","DOI":"10.1023\/A:1008981603178","volume":"9","author":"M Fekkes","year":"2000","unstructured":"Fekkes, M. et al. Development and psychometric evaluation of the TAPQOL: a health-related quality of life instrument for 1\u20135-year-old children. Qual Life Res. 9, 961\u2013972 (2000).","journal-title":"Qual Life Res."},{"key":"28127_CR48","doi-asserted-by":"publisher","first-page":"427","DOI":"10.1111\/epi.13296","volume":"57","author":"MA Ferro","year":"2016","unstructured":"Ferro, M. A., Goodwin, S. W., Sabaz, M. & Speechley, K. N. Measurement equivalence of the newly developed Quality of Life in Childhood Epilepsy Questionnaire (QOLCE\u201055). Epilepsia 57, 427\u2013435 (2016).","journal-title":"Epilepsia"},{"key":"28127_CR49","doi-asserted-by":"publisher","first-page":"864","DOI":"10.1111\/epi.13000","volume":"56","author":"SW Goodwin","year":"2015","unstructured":"Goodwin, S. W., Lambrinos, A. I., Ferro, M. A., Sabaz, M. & Speechley, K. N. Development and assessment of a shortened Quality of Life in Childhood Epilepsy Questionnaire (QOLCE\u201055). Epilepsia 56, 864\u2013872 (2015).","journal-title":"Epilepsia"},{"key":"28127_CR50","doi-asserted-by":"publisher","first-page":"41","DOI":"10.1111\/epi.13254","volume":"57","author":"RJ Kinderen","year":"2016","unstructured":"Kinderen, R. J. et al. An economic evaluation of the ketogenic diet versus care as usual in children and adolescents with intractable epilepsy: an interim analysis. Epilepsia 57, 41\u201350 (2016).","journal-title":"Epilepsia"},{"key":"28127_CR51","doi-asserted-by":"publisher","first-page":"91","DOI":"10.1016\/j.eplepsyres.2017.03.002","volume":"132","author":"BF Wijnen","year":"2017","unstructured":"Wijnen, B. F. et al. Long-term clinical outcomes and economic evaluation of the ketogenic diet versus care as usual in children and adolescents with intractable epilepsy. J Epilepsy Res. 132, 91\u201399 (2017).","journal-title":"J Epilepsy Res."},{"key":"28127_CR52","unstructured":"Achenbach, T. M. & Edelbrock, C. In Burlington (Vt) Vol. 7 (1991)."},{"key":"28127_CR53","doi-asserted-by":"publisher","first-page":"4115","DOI":"10.1016\/j.jchromb.2009.11.004","volume":"877","author":"B De Backer","year":"2009","unstructured":"De Backer, B. et al. Innovative development and validation of an HPLC\/DAD method for the qualitative and quantitative determination of major cannabinoids in cannabis plant material. J. Chromatogr. B. 877, 4115\u20134124 (2009).","journal-title":"J. Chromatogr. B."},{"key":"28127_CR54","doi-asserted-by":"publisher","first-page":"33","DOI":"10.1007\/s11419-016-0330-0","volume":"35","author":"RC Kevin","year":"2017","unstructured":"Kevin, R. C. et al. Urinary cannabinoid levels during nabiximols (Sativex\u00ae)-medicated inpatient cannabis withdrawal. Forensic Toxicol. 35, 33\u201344 (2017).","journal-title":"Forensic Toxicol."},{"key":"28127_CR55","doi-asserted-by":"publisher","first-page":"77","DOI":"10.1191\/1478088706qp063oa","volume":"3","author":"V Braun","year":"2006","unstructured":"Braun, V. & Clarke, V. Using thematic analysis in psychology. Qual Res Psychol. 3, 77\u2013101 (2006).","journal-title":"Qual Res Psychol."},{"key":"28127_CR56","doi-asserted-by":"publisher","first-page":"60","DOI":"10.3102\/10769986025001060","volume":"25","author":"Y Benjamini","year":"2000","unstructured":"Benjamini, Y. & Hochberg, Y. On the adaptive control of the false discovery rate in multiple testing with independent statistics. J. Educ. Behav. Stat 25, 60\u201383 (2000).","journal-title":"J. Educ. Behav. Stat"},{"key":"28127_CR57","unstructured":"Statistics, A. B. o. 2016 Census QuickStats, http:\/\/www.censusdata.abs.gov.au\/census_services\/getproduct\/census\/2016\/quickstat\/036 (2016)."},{"key":"28127_CR58","doi-asserted-by":"crossref","unstructured":"Devinsky, O. et al. Effect of Cannabidiol on Drop Seizures in the Lennox\u2013Gastaut Syndrome. N Engl J Med 378, 1888\u20131897 (2018).","DOI":"10.1056\/NEJMoa1714631"},{"key":"28127_CR59","doi-asserted-by":"publisher","first-page":"1708","DOI":"10.1001\/jama.2017.11909","volume":"318","author":"MO Bonn-Miller","year":"2017","unstructured":"Bonn-Miller, M. O. et al. Labeling accuracy of cannabidiol extracts sold online. JAMA 318, 1708\u20131709 (2017).","journal-title":"JAMA"},{"key":"28127_CR60","unstructured":"ClinicalTrials.gov. Cannabidiol in children with refractory epileptic encephalopathy (care-e), https:\/\/clinicaltrials.gov\/ct2\/show\/record\/NCT03024827?term=cannabinoids&lup_s=09%2F04%2F2017&lup_d=14&show_rss=Y&sel_rss=mod14 (2016)."},{"key":"28127_CR61","doi-asserted-by":"publisher","first-page":"327","DOI":"10.2165\/00003088-200342040-00003","volume":"42","author":"F Grotenhermen","year":"2003","unstructured":"Grotenhermen, F. Pharmacokinetics and pharmacodynamics of cannabinoids. Clinical pharmacokinetics 42, 327\u2013360 (2003).","journal-title":"Clinical pharmacokinetics"},{"key":"28127_CR62","doi-asserted-by":"publisher","first-page":"304","DOI":"10.1016\/j.yebeh.2012.04.128","volume":"24","author":"RS Fisher","year":"2012","unstructured":"Fisher, R. S. et al. Seizure diaries for clinical research and practice: limitations and future prospects. Epilepsy Behav 24, 304\u2013310 (2012).","journal-title":"Epilepsy Behav"},{"key":"28127_CR63","unstructured":"Ferlazzo, E. et al. Methodological issues associated with clinical trials in epilepsy. Expert Rev Clin Pharmacol. 1\u20136 (2017)."},{"key":"28127_CR64","doi-asserted-by":"publisher","first-page":"329","DOI":"10.1002\/ana.24470","volume":"78","author":"DM Goldenholz","year":"2015","unstructured":"Goldenholz, D. M., Moss, R., Scott, J., Auh, S. & Theodore, W. H. Confusing placebo effect with natural history in epilepsy: a big data approach. Ann. Neurol 78, 329\u2013336 (2015).","journal-title":"Ann. Neurol"},{"key":"28127_CR65","doi-asserted-by":"publisher","first-page":"128","DOI":"10.1016\/j.yebeh.2014.12.004","volume":"43","author":"G Zaccara","year":"2015","unstructured":"Zaccara, G., Giovannelli, F. & Schmidt, D. Placebo and nocebo responses in drug trials of epilepsy. Epilepsy Behav 43, 128\u2013134 (2015).","journal-title":"Epilepsy Behav"},{"key":"28127_CR66","doi-asserted-by":"publisher","first-page":"e166","DOI":"10.1371\/journal.pmed.0050166","volume":"5","author":"S Rheims","year":"2008","unstructured":"Rheims, S., Cucherat, M., Arzimanoglou, A. & Ryvlin, P. Greater response to placebo in children than in adults: a systematic review and meta-analysis in drug-resistant partial epilepsy. PLoS Med 5, e166 (2008).","journal-title":"PLoS Med"},{"key":"28127_CR67","doi-asserted-by":"publisher","first-page":"1473","DOI":"10.1212\/WNL.0b013e318232de76","volume":"77","author":"Y Ng","year":"2011","unstructured":"Ng, Y., Conry, J., Drummond, R., Stolle, J. & Weinberg, M. Randomized, phase III study results of clobazam in Lennox-Gastaut syndrome. Neurology 77, 1473\u20131481 (2011).","journal-title":"Neurology"},{"key":"28127_CR68","doi-asserted-by":"publisher","unstructured":"Grelotti, D. J. & Kaptchuk, T. J. Placebo by proxy. BMJ 343, https:\/\/doi.org\/10.1136\/bmj.d4345 (2011).","DOI":"10.1136\/bmj.d4345"},{"key":"28127_CR69","doi-asserted-by":"publisher","first-page":"96","DOI":"10.1038\/pr.2013.66","volume":"74","author":"K Weimer","year":"2013","unstructured":"Weimer, K. et al. Placebo effects in children: a review. Pediatr Res. 74, 96\u2013102 (2013).","journal-title":"Pediatr Res."},{"key":"28127_CR70","doi-asserted-by":"publisher","first-page":"1048","DOI":"10.1056\/NEJMra1407304","volume":"373","author":"D Friedman","year":"2015","unstructured":"Friedman, D. & Devinsky, O. Cannabinoids in the treatment of epilepsy. N Engl J Med 373, 1048\u20131058 (2015).","journal-title":"N Engl J Med"}],"updated-by":[{"DOI":"10.1038\/s41598-018-30164-8","type":"correction","label":"Correction","source":"publisher","updated":{"date-parts":[[2018,8,2]],"date-time":"2018-08-02T00:00:00Z","timestamp":1533168000000}}],"container-title":["Scientific Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41598-018-28127-0.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-018-28127-0","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-018-28127-0.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,12,21]],"date-time":"2022-12-21T07:08:16Z","timestamp":1671606496000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41598-018-28127-0"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,7,5]]},"references-count":70,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2018,12]]}},"alternative-id":["28127"],"URL":"https:\/\/doi.org\/10.1038\/s41598-018-28127-0","relation":{},"ISSN":["2045-2322"],"issn-type":[{"value":"2045-2322","type":"electronic"}],"subject":[],"published":{"date-parts":[[2018,7,5]]},"assertion":[{"value":"24 February 2018","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"4 June 2018","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"5 July 2018","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"2 August 2018","order":4,"name":"change_date","label":"Change Date","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"Correction","order":5,"name":"change_type","label":"Change Type","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has not been fixed in the paper.","order":6,"name":"change_details","label":"Change Details","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"This study was supported by the Lambert Initiative for Cannabinoid Therapeutics, a philanthropically-funded centre for medicinal cannabis research at the University of Sydney. Professor Iain McGregor is Academic Director of the Lambert Initiative and an Australian National Health and Medical Research Council (NHMRC) Principal Research Fellow and receives research funding from the ARC and NHMRC. He is involved in an NHMRC-funded clinical trial using the cannabis extract, Nabiximols (Sativex). He has served as an expert witness in various medicolegal cases involving cannabis and cannabinoids. Professor Nicholas Lintzeris has received funding for unrelated investigator-led research from Indivior and reimbursement for unrelated research activity from Braeburn Pty Ltd. He has also provided paid consultancies for unrelated work from Indivior and Mundipharma. Associate Professor Jonathon Arnold is Associate Director of the Lambert Initiative. He has served as an expert witness in various medicolegal cases involving cannabis and cannabinoids.\u00a0Ms Carol Ireland is a member of the Australian Advisory Council on the Medicinal Use of Cannabis, Steering Committee for Medicinal Cannabis NSW, Refractory Paediatric Epilepsy Steering Committee, and the Lambert Initiative Advisory Board, and is the Director of the Medical Cannabis Council. Dr David Allsop has been a paid consultant for GW Pharmaceuticals. All other authors have no competing financial or non-financial interests to declare.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing Interests"}}],"article-number":"10154"}}