Clinical Outcome Data of Children Treated with Cannabis-Based Medicinal Products for Treatment Resistant Epilepsy—Analysis from the UK Medical Cannabis Registry

Simon Erridge; Carl Holvey; Ross Coomber; Jonathan Hoare; Shaheen Khan; Michael W. Platt; James J. Rucker; Mark W. Weatherall; Sushil Beri; Mikael H. Sodergren

doi:10.1055/a-2002-2119

Neuropediatrics, Inhaltsverzeichnis

CC BY 4.0 · Neuropediatrics 2023; 54(03): 174-181
DOI: 10.1055/a-2002-2119

Original Article

Clinical Outcome Data of Children Treated with Cannabis-Based Medicinal Products for Treatment Resistant Epilepsy—Analysis from the UK Medical Cannabis Registry

Simon Erridge

¹Department of Surgery & Cancer, Imperial College London, London, United Kingdom

²Department of Medicine, Sapphire Medical Clinics, London, United Kingdom

,

Carl Holvey

²Department of Medicine, Sapphire Medical Clinics, London, United Kingdom

,

Ross Coomber

²Department of Medicine, Sapphire Medical Clinics, London, United Kingdom

³Department of Trauma & Orthopaedics, St Georges NHS Healthcare Trust, London, United Kingdom

,

Jonathan Hoare

¹Department of Surgery & Cancer, Imperial College London, London, United Kingdom

²Department of Medicine, Sapphire Medical Clinics, London, United Kingdom

,

Shaheen Khan

²Department of Medicine, Sapphire Medical Clinics, London, United Kingdom

⁴Department of Palliative Medicine, Guy's & St Thomas' NHS Foundation Trust, London, United Kingdom

,

Michael W. Platt

¹Department of Surgery & Cancer, Imperial College London, London, United Kingdom

²Department of Medicine, Sapphire Medical Clinics, London, United Kingdom

,

James J. Rucker

²Department of Medicine, Sapphire Medical Clinics, London, United Kingdom

⁵Department of Psychological Medicine, Institute of Psychiatry, Psychology & Neuroscience, Kings College London, London, United Kingdom

⁶Centre for Affective Disorders, South London & Maudsley NHS Foundation Trust, London, United Kingdom

,

Mark W. Weatherall

²Department of Medicine, Sapphire Medical Clinics, London, United Kingdom

⁷Department of Neurology, Buckinghamshire Healthcare NHS Trust, Amersham, United Kingdom

,

Sushil Beri^*

¹Department of Surgery & Cancer, Imperial College London, London, United Kingdom

²Department of Medicine, Sapphire Medical Clinics, London, United Kingdom

,

Mikael H. Sodergren^*

¹Department of Surgery & Cancer, Imperial College London, London, United Kingdom

²Department of Medicine, Sapphire Medical Clinics, London, United Kingdom

› Institutsangaben

Abstract

Background There is a paucity of high-quality evidence of the efficacy and safety of cannabis-based medicinal products in treatment of treatment-resistant epilepsy (TRE) in children.

Methods A case series of children (<18 years old) with TRE from the UK Medical Cannabis Registry was analyzed. Primary outcomes were ≥50% reduction in seizure frequency, changes in the Impact of Pediatric Epilepsy Score (IPES), and incidence of adverse events.

Results Thirty-five patients were included in the analysis. Patients were prescribed during their treatment with the following: CBD isolate oils (n = 19), CBD broad-spectrum oils (n = 17), and CBD/Δ⁹-THC combination therapy (n = 17). Twenty-three (65.7%) patients achieved a ≥50% reduction in seizure frequency. 94.1% (n = 16) of patients treated with CBD and Δ⁹-THC observed a ≥50% reduction in seizure frequency compared to 31.6% (n = 6) and 17.6% (n = 3) of patients treated with CBD isolates and broad-spectrum CBD products, respectively (p< 0.001). Twenty-six (74.3%) adverse events were reported by 16 patients (45.7%). The majority of these were mild (n = 12; 34.2%) and moderate (n = 10; 28.6%).

Conclusion The results of this study demonstrate a positive signal of improved seizure frequency in children treated with Cannabis-based medicinal products (CBMPs) for TRE. Moreover, the results suggest that CBMPs are well-tolerated in the short term. The limitations mean causation cannot be determined in this open-label, case series.

Keywords

pediatrics - epilepsy - treatment-resistant epilepsy - cannabidiol - tetrahydrocannabinol - cannabis

Volltext

Referenzen

References
1 Fisher RS, Acevedo C, Arzimanoglou A. et al. ILAE official report: a practical clinical definition of epilepsy. Epilepsia 2014; 55 (04) 475-482
2 Ngugi AK, Bottomley C, Kleinschmidt I, Sander JW, Newton CR. Estimation of the burden of active and life-time epilepsy: a meta-analytic approach. Epilepsia 2010; 51 (05) 883-890
3 Fiest KM, Sauro KM, Wiebe S. et al. Prevalence and incidence of epilepsy: a systematic review and meta-analysis of international studies. Neurology 2017; 88 (03) 296-303
4 Devinsky O, Spruill T, Thurman D, Friedman D. Recognizing and preventing epilepsy-related mortality: a call for action. Neurology 2016; 86 (08) 779-786
5 Nordli Jr DR. Special needs of the adolescent with epilepsy. Epilepsia 2001; 42 (s8): 10-17
6 Chen Z, Brodie MJ, 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 2018; 75 (03) 279-286
7 Wiebe S, Blume WT, Girvin JP, Eliasziw M. Effectiveness and Efficiency of Surgery for Temporal Lobe Epilepsy Study Group. A randomized, controlled trial of surgery for temporal-lobe epilepsy. N Engl J Med 2001; 345 (05) 311-318
8 Zou S, Kumar U. Cannabinoid receptors and the endocannabinoid system: signaling and function in the central nervous system. Int J Mol Sci 2018; 19 (03) 833
9 Vega-García A, Feria-Romero I, García-Juárez A. et al. Cannabinoids: a new perspective on epileptogenesis and seizure treatment in early life in basic and clinical studies. Front Behav Neurosci 2021; 14: 610484
10 Vinogradova LV, van Rijn CM. Long-term disease-modifying effect of the endocannabinoid agonist WIN55,212-2 in a rat model of audiogenic epilepsy. Pharmacol Rep 2015; 67 (03) 501-503
11 Cristino L, Bisogno T, Di Marzo V. Cannabinoids and the expanded endocannabinoid system in neurological disorders. Nat Rev Neurol 2020; 16 (01) 9-29
12 de Carvalho Reis R, Almeida KJ, da Silva Lopes L, de Melo Mendes CM, Bor-Seng-Shu E. Efficacy and adverse event profile of cannabidiol and medicinal cannabis for treatment-resistant epilepsy: systematic review and meta-analysis. Epilepsy Behav 2020; 102: 106635
13 Silvestro S, Mammana S, Cavalli E, Bramanti P, Mazzon E. Use of cannabidiol in the treatment of epilepsy: efficacy and security in clinical trials. Molecules 2019; 24 (08) 1459
14 Lattanzi S, Brigo F, Trinka E. et al. Efficacy and safety of cannabidiol in epilepsy: a systematic review and meta-analysis. Drugs 2018; 78 (17) 1791-1804
15 Thiele EA, Bebin EM, Bhathal H. et al; GWPCARE6 Study Group. Add-on cannabidiol treatment for drug-resistant seizures in tuberous sclerosis complex: a placebo-controlled randomized clinical trial. JAMA Neurol 2021; 78 (03) 285-292
16 Nabbout R, Thiele EA. The role of cannabinoids in epilepsy treatment: a critical review of efficacy results from clinical trials. Epileptic Disord 2020; 22 (S1): 23-28
17 Lattanzi S, Trinka E, Striano P. et al. Highly purified cannabidiol for epilepsy treatment: a systematic review of epileptic conditions beyond Dravet syndrome and Lennox-Gastaut syndrome. CNS Drugs 2021; 35 (03) 265-281
18 Bow EW, Rimoldi JM. The structure–function relationships of classical cannabinoids: CB1/CB2 modulation. Perspect Medicin Chem 2016; 8: 17-39
19 Whalley BJ, Lin H, Bell L. et al. Species-specific susceptibility to cannabis-induced convulsions. Br J Pharmacol 2019; 176 (10) 1506-1523
20 Anderson LL, Low IK, McGregor IS, Arnold JC. Interactions between cannabidiol and Δ⁹ -tetrahydrocannabinol in modulating seizure susceptibility and survival in a mouse model of Dravet syndrome. Br J Pharmacol 2020; 177 (18) 4261-4274
21 Anderson LL, Etchart MG, Bahceci D, Golembiewski TA, Arnold JC. Cannabis constituents interact at the drug efflux pump BCRP to markedly increase plasma cannabidiolic acid concentrations. Sci Rep 2021; 11 (01) 14948
22 Press CA, Knupp KG, Chapman KE. Parental reporting of response to oral cannabis extracts for treatment of refractory epilepsy. Epilepsy Behav 2015; 45: 49-52
23 Tzadok M, Uliel-Siboni S, Linder I. et al. CBD-enriched medical cannabis for intractable pediatric epilepsy: the current Israeli experience. Seizure 2016; 35: 41-44
24 Erridge S, Salazar O, Kawka M. et al. An initial analysis of the UK Medical Cannabis Registry: outcomes analysis of first 129 patients. Neuropsychopharmacol Rep 2021; 41 (03) 362-370
25 Kwan P, Arzimanoglou A, Berg AT. et al. Definition of drug resistant epilepsy: consensus proposal by the ad hoc Task Force of the ILAE Commission on Therapeutic Strategies. Epilepsia 2010; 51 (06) 1069-1077
26 Case P. The NICE guideline on medicinal cannabis: keeping Pandora's box shut tight?. Med Law Rev 2020; 28 (02) 401-411
27 Medicines & Healthcare Products Regulatory Agency. The supply, manufacture, importation and distribution of unlicensed cannabis-based products for medicinal use in humans ‘specials.’ Available from: [Last Accessed: 16th January 2023] 2020 https://assets.publishing.service.gov.uk/government/uploads/system/uploads/attachment_data/file/869284/Cannabis_Guidance__unlicensed_CBPMs__updated_2020.pdf
28 Brusselaers N, Lagergren J. The Charlson comorbidity index in registry-based research. Methods Inf Med 2017; 56 (05) 401-406
29 Mohanraj R, Brodie MJ. Measuring the efficacy of antiepileptic drugs. Seizure 2003; 12 (07) 413-443
30 Camfield C, Breau L, Camfield P. Impact of pediatric epilepsy on the family: a new scale for clinical and research use. Epilepsia 2001; 42 (01) 104-112
31 US Department of Health and Human Services. Common Terminology Criteria for Adverse Events (CTCAE) v4. 03. Washington, DC: US Department of Health and Human Services; 2010
32 Hu TY, Wang HQ, Zhang WP. et al. Network meta-analysis of antiepileptic drugs in focal drug-resistant epilepsy. Epilepsy Res 2020; 167: 106433
33 Beyenburg S, Stavem K, Schmidt D. Placebo-corrected efficacy of modern antiepileptic drugs for refractory epilepsy: systematic review and meta-analysis. Epilepsia 2010; 51 (01) 7-26
34 Brodie MJ, Czapinski P, Pazdera L. et al; GWEP1330 Study Group. A phase 2 randomized controlled trial of the efficacy and safety of Cannabidivarin as add-on therapy in participants with inadequately controlled focal seizures. Cannabis Cannabinoid Res 2021; 6 (06) 528-536
35 Gertsch J. The intricate influence of the placebo effect on medical cannabis and cannabinoids. Med Cannabis Cannabinoids 2018; 1 (01) 60-64
36 Ben-Zeev B. Medical cannabis for intractable epilepsy in childhood: a review. Rambam Maimonides Med J 2020; 11 (01) e0004
37 Zhu HL, Wan JB, Wang YT. et al. Medicinal compounds with antiepileptic/anticonvulsant activities. Epilepsia 2014; 55 (01) 3-16
38 Helmstaedter C, Witt JA. Epilepsy and cognition - a bidirectional relationship?. Seizure 2017; 49: 83-89
39 Banerjee R, Erridge S, Salazar O. et al. Real world evidence in medical cannabis research. Ther Innov Regul Sci 2022; 56 (01) 8-14
40 Gaitatzis A, Sander JW. The long-term safety of antiepileptic drugs. CNS Drugs 2013; 27 (06) 435-455
41 Kellogg M, Meador KJ. Neurodevelopmental effects of antiepileptic drugs. Neurochem Res 2017; 42 (07) 2065-2070

Zusatzmaterial

Supplementary Material