PRIMENA KANABINIODA U LEČENJU EPILEPSIJE: AKTUELNI DOKAZI O EFIKASNOSTI I BEZBEDNOSTI
Sažetak
Činjenica da kod jedne trećine osoba sa epilepsijom ne postoji adekvatna kontrola napada uprkos primeni odgovarajuće farmakoterapije motivisala je istraživanja novih terapijskih opcija. U poslednje dve decenije zabeleženno je povećanje interesovanja za proučavanje terapijskih potencijala kanabinoida za lečenje epilepsije. Na tržištu su dostupni razni preparati bazirani na kanabisu; oni znatno variraju po sastavu i kvalitetu, a njihova primena udružena je sa različitim rizicima. Jedini kanabinoid o čijim prednostima upotrebe trenutno postoje naučni dokazi, dobijeni nakon procene benefita i rizika, jeste kanabidiol (engl. Cannabidiol – CBD). Kanabidiol se razlikuje od drugih kanabinoida po tome što postoje dokazi o njegovoj konstantnoj efikasnosti i o odsustvu psihoaktivnih efekata. Visoko prečišćeni oblik CBD-a prva je supstanca dobijena od biljke kanabisa koja je dobila odobrenje regulatornih agencija Sjedinjenih Američkih Država i Evropske Unije za lečenje napada rezistentnih na farmakoterapiju koji su udruženi sa retkim i teškim epileptičkim sindromima koji su se pojavili u detinjstvu. Kratkoročni neželjeni efekti blagog su i umerenog stepena i popravljaju se nakon prilagođavanja doze. Da bi se otkrili precizni mehanizmi terapijskih efekata, procenila efikasnost CBD-a i u drugim vrstama epilepsije, izvršilo direktno poređenje sa drugim antiepileptičkim lekovima i procenila dugotrajna bezbednost njegove upotrebe, neophodno je sprovesti dalja istraživanja.
Reference
American Academy of Neurology. Position statement: Use of medical cannabis for neurologic disorders [Internet]. Minneapolis (MN): American Academy of Neurology; 2018 [cited 2023 Dec 15]. Available from: https://www.aan.com/siteassets/home-page/policy-and-guidelines/policy/position-statements/cannabis-position-statement.pdf.
Ames FR, Cridland S. Anticonvulsant effect of cannabidiol. Afr Med J 1986;69(1):14. [PubMed]
Assareh N, Gururajan A, Zhou C, Luo JL, Kevin RC, Arnold JC. Cannabidiol disrupts conditioned fear expression and cannabidiolic acid reduces trauma-induced anxiety-related behaviour in mice. Behavioural pharmacology 2020;31(6):591-596. [CrossRef][PubMed]
Azevedo M, Benbadis SR. Efficacy of highly purified cannabidiol (CBD) in typical absence seizures: A pilot study. Epilepsy & Behavior 2023;149:109512. [CrossRef][PubMed]
Bergmann KR, Broekhuizen K, Groeneveld GJ. Clinical trial simulations of the interaction between cannabidiol and clobazam and effect on drop‐seizure frequency. Br J Clin Pharmacol 2020;86(2):380-385. [CrossRef][PubMed]
Bialer M, Perucca E. Does cannabidiol have antiseizure activity independent of its interactions with clobazam? An appraisal of the evidence from randomized controlled trials. Epilepsia 2020;61(6):1082-1089. [CrossRef][PubMed]
Bonn-Miller MO, Loflin MJ, Thomas BF, Marcu JP, Marcu JP, Hyke T, et al. Labeling accuracy of cannabidiol extracts sold online. JAMA 2017;318(17):1708-1709. [CrossRef][PubMed]
Bonomo Y, Souza J, Jackson A, Crippa J, Solowij N. Clinical issues in cannabis use. Br J Clin Pharmacol 2018;84(11):2495-2498. [CrossRef][PubMed]
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(3):279-286. [CrossRef][PubMed]
Chesney E, Oliver D, Green A, Sovi S, Wilson J, Englund A, et al. Adverse effects of cannabidiol: a systematic review and meta-analysis of randomized clinical trials. Neuropsychopharmacology 2020;45(11):1799-1806. [CrossRef][PubMed]
Chesney E, Oliver D, Green A, Sovi S, Wilson J, Englund A, et al. Adverse effects of cannabidiol: a systematic review and meta-analysis of randomized clinical trials. Neuropsychopharmacology 2020;45(11):1799-1806. [CrossRef][PubMed]
Cross JH, Cock H. A perspective on cannabinoids for treating epilepsy: Do they really change the landscape?. Neuropharmacology 2020;170:107861. [CrossRef][PubMed]
Cunha JM, Carlini EA, Pereira AE, Ramos OL, Pimentel C, Gagliardi R, et al. Chronic administration of cannabidiol to healthy volunteers and epileptic patients. Pharmacology 1980;21(3):175-185. [CrossRef][PubMed]
Devane WA, Hanuš L, Breuer A, Pertwee RG, Stevenson LA, Griffin G, et al. Isolation and structure of a brain constituent that binds to the cannabinoid receptor. Science 1992;258(5090):1946-1949. [CrossRef][PubMed]
Devinsky O, Cilio MR, Cross H, Fernandez-Ruiz J, French J, Hill C, et al. Cannabidiol: pharmacology and potential therapeutic role in epilepsy and other neuropsychiatric disorders. Epilepsia 2014;55(6):791-802. [CrossRef][PubMed]
Devinsky O, Cross JH, Laux L, Marsh E, Miller I, Nabbout R, et al. Trial of cannabidiol for drug-resistant seizures in the Dravet syndrome. N Engl J Med 2017;376(21):2011-2020. [CrossRef][PubMed]
Devinsky O, Nabbout R, Miller I, Laux L, Zolnowska M, Wright S, et al. Long-term cannabidiol treatment in patients with Dravet syndrome: an open-label extension trial. Epilepsia 2019;60(2):294-302. [CrossRef][PubMed]
Devinsky O, Patel AD, Cross JH, Villanueva V, Wirrell EC, Privitera M, et al. Effect of cannabidiol on drop seizures in the Lennox-Gastaut syndrome. N Engl J Med 2018;378(20):1888-1897. [CrossRef][PubMed]
Devinsky O, Thiele EA, Wright S, Checketts D, Morrison G, Dunayevich E, et al. Cannabidiol efficacy independent of clobazam: Meta-analysis of four randomized controlled trials. Acta Neurol Scand 2020;142(6):531-540. [CrossRef][PubMed]
Dryburgh LM, Bolan NS, Grof C, Galettis P, Schneider J, Lucas C, et al. Cannabis contaminants: sources, distribution, human toxicity and pharmacologic effects. Br J Clin Pharmacol 2018;84(11):2468-2476. [CrossRef][PubMed]
European Medical Agency. From laboratory to patient: the journey of a centrally authorised medicine [Internet]. London: EMA; 2019 [cited 2023 Dec 15]. Available from: https://www.ema.europa.eu/en/documents/other/laboratory-patient-journey-centrally-authorised-medicine_en.pdf.
European Medicines Agency. Epidyolex: EPAR – Product information [Internet]. London: EMA; 2019 [cited 2023 Dec 15]. Available from: https://www.ema.europa.eu/en/medicines/human/EPAR/epidyolex.
European Monitoring Centre for Drugs and Drug Addiction. Medical use of cannabis and cannabinoids: questions and answers for policymaking [Internet]. Luxembourg: Publications Office of the European Union; 2018 [cited 2023 Dec ]. Available from: https://www.euda.europa.eu/system/files/publications/10171/20185584_TD0618186ENN_PDF.pdf.
Fisher RS, Van Emde Boas W, Blume W, Elger C, Genton P, Lee P, et al. Epileptic seizures and epilepsy: definitions proposed by the International League Against Epilepsy (ILAE) and the International Bureau for Epilepsy (IBE). Epilepsia 2005;46(4):470-472. [CrossRef][PubMed]
Franco V, Perucca E. Pharmacological and therapeutic properties of cannabidiol for epilepsy. Drugs 2019;79(13):1435-1454. [CrossRef][PubMed]
Freeman TP, Groshkova T, Cunningham A, Sedefov R, Griffiths P, Lynskey MT. Increasing potency and price of cannabis in Europe, 2006-16. Addiction 2019;114(6):1015-1023. [CrossRef][PubMed]
Friedman D, Devinsky O. Cannabinoids in the treatment of epilepsy. N Engl J Med 2015;373(11):1048-1058. [CrossRef][PubMed]
Friedman D, Sirven JI. Historical perspective on the medical use of cannabis. Epilepsy Behav 2017;70(PtB):298-301. [CrossRef][PubMed]
Gloss D, Vickrey B. Cannabinoids for epilepsy. The Cochrane database of systematic reviews 2014;2014(3):CD009270. [CrossRef][PubMed]
Gray RA, Whalley BJ. The proposed mechanisms of action of CBD in epilepsy. Epileptic Disord 2020;22(S1):10-15. [CrossRef][PubMed]
Groeneveld GJ, Martin JH. Parasitic pharmacology: A plausible mechanism of action for cannabidiol. Br J Clin Pharmacol 2020;86(2):189-191. [CrossRef][PubMed]
Gross DW, Hamm J, Ashworth NL, Quigley D. Marijuana use and epilepsy: prevalence in patients of a tertiary care epilepsy center. Neurology 2004;62(11):2095-2097. [CrossRef][PubMed]
Hauser AW. Questioning the effectiveness of newer antiseizure medications. JAMA Neurol 2018;75(3):273–274. [CrossRef][PubMed]
Hazekamp A. The trouble with CBD Oil. Med Cannabis Cannabinoids 2018;1(1):65-72. [CrossRef][PubMed]
Hindley G, Beck K, Borgan F. Psychiatric symptoms caused by cannabis constituents: a systematic review and meta-analysis. Lancet Psychiatry 2020;7(4):344-353. [CrossRef][PubMed]
Irwig L, Irwig J, Trevena L, Sweet M, editors. Smart health choices: Making sense of health advice London: Hammersmith Press; 2008.
Klein BD, Jacobson CA, Metcalf CS, Smith MD, Wilcox KS, Hampson AJ, et al. Evaluation of cannabidiol in animal seizure models by the epilepsy therapy screening program (ETSP). Neurochem Res 2017;42(7):1939-1948. [CrossRef][PubMed]
Koppel BS, Brust JCM, Fife T, Bronstein J, Youssof S, Gronseth G, et al. Systematic review: efficacy and safety of medical marijuana in selected neurologic disorders: report of the Guideline Development Subcommittee of the American Academy of Neurology. Neurology 2014;82(17):1556-1563. [CrossRef][PubMed]
Lattanzi S, Brigo F, Trinka E, Zaccara G, Cagnetti C, Del Giovane C, et al. Efficacy and safety of cannabidiol in epilepsy: A systematic review and meta-analysis. Drugs 2018;78(17):1791-1804. [CrossRef][PubMed]
Lattanzi S, Trinka E, Striano P, Zaccara G, Del Giovane C, Nardone R, et al. Cannabidiol efficacy and clobazam status: A systematic review and meta-analysis. Epilepsia 2020;61(6):1090-1098. [CrossRef][PubMed]
Liebling JP, Clarkson NJ, Gibbs BW, Yates AS, O'Sullivan SE. An analysis of over-the-counter cannabidiol products in the United Kingdom. Cannabis Cannabinoid Res 2020;7(2):207-213. [CrossRef][PubMed]
Maa E, Figi P. The case for medical marijuana in epilepsy. Epilepsia 2014;55(6):783-786. [CrossRef][PubMed]
Martin JH, Schneider J, Lucas CJ, Galettis P. Exogenous cannabinoid efficacy: Merely a pharmacokinetic interaction?. Clin Pharmacokinet 2018;57(5):539-545. [CrossRef][PubMed]
Mechoulam R, Shani A, Edery H, Grunfeld Y. Chemical basis of hashish activity. Science 1970;169(3945):611-612. [CrossRef][PubMed]
Miller I, Scheffer IE, Gunning B, Sanchez-Carpintero R, Gil-Nagel A, Perry MS, et al. Dose-ranging effect of adjunctive oral cannabidiol vs placebo on convulsive seizure frequency in Dravet syndrome. JAMA Neurology 2020;77(5):613-621. [CrossRef][PubMed]
Morales P, Hurst DP, Reggio PH. Molecular targets of the phytocannabinoids: A complex picture. Prog Chem Org Nat Prod 2017;103:103-131. [CrossRef][PubMed]
Pertwee RG. The diverse CB1 and CB2 receptor pharmacology of three plant cannabinoids: delta9-tetrahydrocannabinol, cannabidiol and delta9-tetrahydrocannabivarin. Br J Pharmacol 2008;153(2):199-215. [CrossRef][PubMed]
Perucca E, Perucca P, White HS, Wirrell EC. Drug resistance in epilepsy. Lancet Neurol 2023;22(8):723-734. [CrossRef][PubMed]
Porter BE, Jacobson C. Report of a parent survey of cannabidiol-enriched cannabis use in pediatric treatment-resistant epilepsy. Epilepsy Behav 2013;29(3):574-577. [CrossRef][PubMed]
Potter DJ. A review of the cultivation and processing of cannabis (Cannabis sativa L.) for production of prescription medicines in the UK. Drug Test Anal 2014;6(1-2):31-38. [CrossRef][PubMed]
Pratt M, Stevens A, Thuku M, Butler C, Skidmore B, Wieland LS, et al. Benefits and harms of medical cannabis: a scoping review of systematic reviews. Syst Rev 2019;8(1):320. [CrossRef][PubMed]
Schlag A. An evaluation of regulatory regimes of medical cannabis: what lessons can be learned for the UK?. Med Cannabis Cannabinoids 2020;3(1):76-83. [CrossRef][PubMed]
Senn L, Cannazza G, Biagini G. Receptors and channels possibly mediating the effects of phytocannabinoids on seizures and epilepsy. Pharmaceuticals (Basel) 2020;13(8):174. [CrossRef][PubMed]
Thiele EA, Bebin EM, Bhathal H, Jansen FE, Kotulska K, Lawson JA, et al. Add-on cannabidiol treatment for drug-resistant seizures in tuberous sclerosis complex. JAMA Neurol 2021;78(3):285-292. [CrossRef][PubMed]
Thiele EA, Marsh ED, French JA, Mazurkiewicz-Beldzinska M, Benbadis SR, Joshi C, et al. Cannabidiol in patients with seizures associated with Lennox-Gastaut syndrome (GWPCARE4): a randomised, double-blind, placebo-controlled phase 3 trial. Lancet 2018;391(10125):1085-1096. [CrossRef][PubMed]
U.S. Food and Drug Administration. FDA approves first drug comprised of an active ingredient derived from marijuana to treat rare, severe forms of epilepsy [Internet]. Silver Spring (MD): FDA; 2018 [cited 2023 Dec 15]. Available from: https://www.fda.gov/news-events/press-announcements/fda-approves-first-drug-comprised-active-ingredient-derived-marijuana-treat-rare-severe-forms.
U.S. Food and Drug Administration. What you need to know (and what we’re working to find out) about products containing cannabis or cannabis-derived compounds [Internet]. Silver Spring (MD): FDA; 2019 [cited 2023 Dec 15]. Available from: https://www.fda.gov/consumers/consumer-updates/what-you-need-know-and-what-were-working-find-out-about-products-containing-cannabis-or-cannabis.
Volkow ND, Baler RD, Compton WM, Weiss SR. Adverse health effects of marijuana use. N Engl J Med 2014;370(23):2219-2227. [CrossRef][PubMed]
World Health Organization. The health and social effects of nonmedical cannabis use [Internet]. Geneva: World Health Organization; 2016 [cited 2023 Dec 15]. Available from: https://iris.who.int/handle/10665/251056.
