Skip to main content
SpringerLink
Log in

Cannabis-based magistral formulation is highly effective as an adjuvant treatment in drug-resistant focal epilepsy in adult patients: an open-label prospective cohort study

Neurological Sciences volume 44, pages 297–304 (2023)Cite this article

Abstract  

Introduction

The safety and efficacy of a formulation high in cannabidiol (CBD) and low in ∆9-tetrahydrocannabinol (THC) to treat drug-resistant epilepsy have been examined previously in children, but not in adult population. The aim of this study was to evaluate whether CBD-rich oil, as an add-on treatment to conventional antiepileptic drugs, was effective, safe, and well-tolerated in adults with drug-resistant focal epilepsy (DRFE).

Methods

An open-label, prospective cohort, single-center in adult patients with DRFE, were receiving stable doses of antiepileptic drugs (AEDs). A cannabis based-magistral formulation (CBMF) (100 mg/ml CBD and THC <1.9 mg/ml) was administrated 0.1 ml sublingually every 12 hours, up-titrated weekly. The primary outcome was to establish a reduction in seizures frequency >50% at 12 weeks. Adverse-drug reactions monitoring was done. p-value <0.05 was statistically significant.

Results

Between August 2020 and July 2022, 44 (38.6%) patients completed >3 months of follow-up. The median daily dose of CBD was 200 mg, that of THC was 4 mg, and that of CBD per kilogram of weight was 3.7 mg. The median number of seizures per month before CBD treatment was 11, and after CBD treatment was 2.5 (p<0.001). A reduction in seizures >50% at 12 week was achieved in 79.5% of the patients. The median percentage change in seizure frequency per month was 84.1% at 12 weeks. Five patients reported any adverse-drug reactions.

Conclusion

The CBMF is a highly effective and safety therapy to treat adult patients with DRFE. The reduction in seizures frequency is maintained over time.

This is a preview of subscription content, access via your institution.

Access options

Buy single article

Instant access to the full article PDF.

USD 39.95

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Fig. 1
Fig. 2
Fig. 3

References

  1. Devinsky O, Cross JH, Laux L et al (2017) Trial of cannabidiol for drug-resistant seizures in the Dravet syndrome. N Engl J Med 376:2011–2020. https://doi.org/10.1056/NEJMoa1611618

    Article  CAS  Google Scholar 

  2. Devinsky O, Patel AD, Thiele EA et al (2018) Randomized, dose-ranging safety trial of cannabidiol in Dravet syndrome. Neurology 90:e1204–e1211. https://doi.org/10.1212/WNL.0000000000005254

    Article  CAS  Google Scholar 

  3. Devinsky O, Patel AD, Cross JH et al (2018) Effect of cannabidiol on drop seizures in the Lennox-Gastaut syndrome. N Engl J Med 378:1888–1897. https://doi.org/10.1056/NEJMoa1714631

    Article  CAS  Google Scholar 

  4. Thiele EA, Marsh ED, French JA et al (2018) Cannabidiol in patients with seizures associated with Lennox-Gastaut syndrome (GWPCARE4): a randomised, double-blind, placebo-controlled phase 3 trial. Lancet 391:1085–1096. https://doi.org/10.1016/S0140-6736(18)30136-3

    Article  CAS  Google Scholar 

  5. Thiele EA, Bebin EM, Bhathal H et al (2021) Add-on cannabidiol treatment for drug-resistant seizures in tuberous sclerosis complex. JAMA Neurol 78:285. https://doi.org/10.1001/jamaneurol.2020.4607

    Article  Google Scholar 

  6. Devinsky O, Verducci C, Thiele EA et al (2018) Open-label use of highly purified CBD (Epidiolex®) in patients with CDKL5 deficiency disorder and Aicardi, Dup15q, and Doose syndromes. Epilepsy Behav 86:131–137. https://doi.org/10.1016/j.yebeh.2018.05.013

    Article  Google Scholar 

  7. Kuchenbuch M, D’Onofrio G, Chemaly N et al (2020) Add-on cannabidiol significantly decreases seizures in 3 patients with SYNGAP1 developmental and epileptic encephalopathy. Epilepsia Open 5:496–500. https://doi.org/10.1002/epi4.12411

    Article  Google Scholar 

  8. Lattanzi S, Trinka E, Striano P et al (2021) Highly purified cannabidiol for epilepsy treatment: a systematic review of epileptic conditions beyond Dravet syndrome and Lennox-Gastaut syndrome. CNS Drugs 35:265–281. https://doi.org/10.1007/s40263-021-00807-y

    Article  Google Scholar 

  9. Devinsky O, Cilio MR, Cross H et al (2014) Cannabidiol: pharmacology and potential therapeutic role in epilepsy and other neuropsychiatric disorders. Epilepsia 55:791–802. https://doi.org/10.1111/epi.12631

    Article  CAS  Google Scholar 

  10. McCoy B, Wang L, Zak M et al (2018) A prospective open-label trial of a CBD/THC cannabis oil in dravet syndrome. Ann Clin Transl Neurol 5:1077–1088. https://doi.org/10.1002/acn3.621

    Article  CAS  Google Scholar 

  11. Caraballo R, Reyes G, Demirdjian G et al (2022) Long-term use of cannabidiol-enriched medical cannabis in a prospective cohort of children with drug-resistant developmental and epileptic encephalopathy. Seizure 95:56–63. https://doi.org/10.1016/j.seizure.2022.01.001

    Article  Google Scholar 

  12. McNamara NA, Dang LT, Sturza J et al (2020) Thrombocytopenia in pediatric patients on concurrent cannabidiol and valproic acid. Epilepsia 61:1–5. https://doi.org/10.1111/epi.16596

    Article  CAS  Google Scholar 

  13. Gunning B, Mazurkiewicz-Bełdzińska M, Chin RFM et al (2021) Cannabidiol in conjunction with clobazam: analysis of four randomized controlled trials. Acta Neurol Scand 143:154–163. https://doi.org/10.1111/ane.13351

    Article  CAS  Google Scholar 

  14. Moreno-Sanz G, Madiedo A, Hernandez P, et al (2022) Sex-dependent prescription patterns and clinical outcomes associated with the use of two oral cannabis formulations in the multimodal management of chronic pain patients in Colombia. Front Pain Res 3. https://doi.org/10.3389/fpain.2022.854795

  15. Devinsky O, Marsh E, Friedman D et al (2016) Cannabidiol in patients with treatment-resistant epilepsy: an open-label interventional trial. Lancet Neurol 15:270–278. https://doi.org/10.1016/S1474-4422(15)00379-8

    Article  CAS  Google Scholar 

  16. Carreño M, Donaire A, Falip M et al (2009) Validation of the Spanish version of the Liverpool Adverse Events Profile in patients with epilepsy. Epilepsy Behav 15:154–159. https://doi.org/10.1016/j.yebeh.2008.11.016

    Article  Google Scholar 

  17. Patel S, Grinspoon R, Fleming B et al (2021) The long-term efficacy of cannabidiol in the treatment of refractory epilepsy. Epilepsia 62:1594–1603. https://doi.org/10.1111/epi.16936

    Article  CAS  Google Scholar 

  18. Gaston TE, Ampah SB, Martina Bebin E et al (2021) Long-term safety and efficacy of highly purified cannabidiol for treatment refractory epilepsy. Epilepsy Behav 117:107862. https://doi.org/10.1016/j.yebeh.2021.107862

    Article  Google Scholar 

  19. Strickland JC, Jackson H, Schlienz NJ et al (2021) Cross-sectional and longitudinal evaluation of cannabidiol (CBD) product use and health among people with epilepsy. Epilepsy Behav 122:108205. https://doi.org/10.1016/j.yebeh.2021.108205

    Article  Google Scholar 

  20. Malaca S, Gottardi M, Pigliasco F, et al (2021) UHPLC-MS/MS Analysis of cannabidiol and its metabolites in serum of patients with resistant epilepsy treated with CBD formulations. Pharmaceuticals (Basel) 14:630. https://doi.org/10.3390/ph14070630

  21. Gray RA, Whalley BJ (2020) The proposed mechanisms of action of CBD in epilepsy. Epileptic Disord 22:10–15. https://doi.org/10.1684/epd.2020.1135

    Article  Google Scholar 

  22. Rocha L, Frías-Soria CL, Ortiz JG et al (2020) Is cannabidiol a drug acting on unconventional targets to control drug-resistant epilepsy? Epilepsia Open 5:36–49. https://doi.org/10.1002/epi4.12376

    Article  Google Scholar 

  23. de Boleti AP, A, Frihling BEF, e Silva PS, et al (2022) Biochemical aspects and therapeutic mechanisms of cannabidiol in epilepsy. Neurosci Biobehav Rev 132:1214–1228. https://doi.org/10.1016/j.neubiorev.2020.09.027

    Article  Google Scholar 

  24. Grayson L, Ampah S, Hernando K et al (2021) Longitudinal impact of cannabidiol on EEG measures in subjects with treatment-resistant epilepsy. Epilepsy Behav 122:108190. https://doi.org/10.1016/j.yebeh.2021.108190

    Article  Google Scholar 

  25. Herlopian A, Barnett JR, Nascimento FA et al (2022) Electroencephalographic changes in purified pharmaceutical cannabidiol therapy. Epilepsy Behav 128:108558. https://doi.org/10.1016/j.yebeh.2022.108558

    Article  Google Scholar 

  26. Devinsky O, Marmanillo A, Hamlin T et al (2022) Observational study of medical marijuana as a treatment for treatment-resistant epilepsies. Ann Clin Transl Neurol 9:497–505. https://doi.org/10.1002/acn3.51537

    Article  CAS  Google Scholar 

  27. Marchese F, Vari MS, Balagura G et al (2022) An open retrospective study of a standardized cannabidiol based-oil in treatment-resistant epilepsy. Cannabis Cannabinoid Res 7:199–206. https://doi.org/10.1089/can.2019.0082

    Article  Google Scholar 

  28. Szaflarski JP, Bebin EM, Cutter G et al (2018) Cannabidiol improves frequency and severity of seizures and reduces adverse events in an open-label add-on prospective study. Epilepsy Behav 87:131–136. https://doi.org/10.1016/j.yebeh.2018.07.020

    Article  Google Scholar 

  29. D’Onofrio G, Kuchenbuch M, Hachon-Le Camus C et al (2020) Slow titration of cannabidiol add-on in drug-resistant epilepsies can improve safety with maintained efficacy in an open-label study. Front Neurol 11:1–11. https://doi.org/10.3389/fneur.2020.00829

    Article  Google Scholar 

  30. Lattanzi S, Trinka E, Striano P et al (2020) Cannabidiol efficacy and clobazam status: A systematic review and meta-analysis. Epilepsia 61:1090–1098. https://doi.org/10.1111/epi.16546

    Article  CAS  Google Scholar 

  31. Gaston TE, Bebin EM, Cutter GR et al (2017) Interactions between cannabidiol and commonly used antiepileptic drugs. Epilepsia 58:1586–1592. https://doi.org/10.1111/epi.13852

    Article  CAS  Google Scholar 

  32. Landmark CJ, Brandl U (2020) Pharmacology and drug interactions of cannabinoids. Epileptic Disord 22:16–22. https://doi.org/10.1684/epd.2019.1123

    Article  Google Scholar 

  33. Savage TE, Sourbron J, Bruno PL et al (2020) Efficacy of cannabidiol in subjects with refractory epilepsy relative to concomitant use of clobazam. Epilepsy Res 160:106263. https://doi.org/10.1016/j.eplepsyres.2019.106263

    Article  Google Scholar 

  34. Gilmartin CGS, Dowd Z, Parker APJ, Harijan P (2021) Interaction of cannabidiol with other antiseizure medications: a narrative review. Seizure 86:189–196. https://doi.org/10.1016/j.seizure.2020.09.010

    Article  Google Scholar 

  35. Arzimanoglou A, Brandl U, Cross JH et al (2020) Epilepsy and cannabidiol: a guide to treatment. Epileptic Disord 22:1–14. https://doi.org/10.1684/epd.2020.1141

    Article  Google Scholar 

  36. Nair DR (2016) Management of drug-resistant epilepsy. Continuum (Minneap Minn) 22:157–172. https://doi.org/10.1212/CON.0000000000000297

    Article  Google Scholar 

Download references

Acknowledgements

To patients and their families who agreed to participate in this observational study.

Funding

This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.

Author information

Authors and Affiliations

  1. Unit of Clinical Neurology, School of Medicine, Universidad Nacional de Colombia, Bogotá, Colombia

    Cristian Eduardo Navarro

  2. Master’s Program in Epidemiology, School of Medicine, Universidad El Bosque, Bogotá, Colombia

    Cristian Eduardo Navarro

  3. Grupo de Investigación en Neurología, de la Universidad Nacional de Colombia–NeuroUnal, Bogotá, Colombia

    Cristian Eduardo Navarro

  4. Medical Cannabis and Drug-Resistant Epilepsy Program, Clínica Zerenia, Bogotá, Colombia

    Cristian Eduardo Navarro

Authors
  1. Cristian Eduardo Navarro
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

Cristian Eduardo Navarro MD MSc: conceptualization, review of literature, data collection, data analysis, writing, and editing the manuscript. The author read and approved the final manuscript.

Corresponding author

Correspondence to Cristian Eduardo Navarro.

Ethics declarations

Ethical approval

The institutional review board approved the study.

Consent to participate and for publication

Patients provided written informed consent to participate and to use a cannabis-based magistral formulation (CBMF).

Conflict of interest

Cristian Eduardo Navarro MD MSc works at Clínica Zerenia in Bogotá (Colombia) which is a reference center specializing in medical cannabis therapy owned by Khiron Life Science Corp®. Khiron Life Science Corp.® manufactures the cannabis-based magistral formulation used in this study.

Informed consent

Informed consent was provided by each patient at the beginning of the study.

Additional information

Publisher's note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Springer Nature or its licensor holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and Permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Navarro, C.E. Cannabis-based magistral formulation is highly effective as an adjuvant treatment in drug-resistant focal epilepsy in adult patients: an open-label prospective cohort study. Neurol Sci 44, 297–304 (2023). https://doi.org/10.1007/s10072-022-06393-1

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10072-022-06393-1

Keywords

search

Navigation