ST JAMES’ HOSPITAL
DEPARTMENT OF NEUROLOGY
HOSPITAL 5, HEALTH CARE CENTRE
TELEPHONE: 4103688 Fax: 4103477
email [email protected] & [email protected]
MedicinalCannabisforthetreatmentofEpilepsy–OpeningStatementtotheOireachtas
HealthCommittee
ColinDohertyMD
ConsultantEpileptologist,StJames’sHospital,Dublin8
Introduction
Goodmorning,mynameisColinDoherty,IamaConsultantNeurologistfromStJames’sHospital
inDublinwithexpertiseintreatmentallformsofepilepsy.IamthenationalClinicalLeadforthe
EpilepsyProgrammeinIrelandandSeniorLectureratTrinityCollegeSchoolofMedicineanda
memberoftheInternationalLeagueAgainstEpilepsy(ILAE).InthefollowingIwillgiveabrief
reviewofthehistoryofcannabisuseforepilepsyanddescribethescienceunderlyingits
potentialuseaprescribedtreatment.Finally,Iwillattempttooutlineapathwayfordevelopinga
consensusaroundpotentialprescribingpractice.
HistoryofCannabisuseforEpilepsy
Whiletherearereferencestomedicalusesofhempgoingback8,000yearsinChina,Irish
physicianW.B.O’Shaughnessyiswidelyacknowledgedtohavewrittenthefirstmodernscientific
paperonMedicinalUseofCannabisinthe‘ProvincialMedicalJournal’publishedin1843.
O’ShaughnessywasborninLimerickin1809andmovedtoCalcuttawiththeEastIndiaCompany
whereheobservedthelocaluseofcannabisforvariousailments.Heisnowconsideredthe
fatherofthemedicinalcannabismovement.
In1851,afterO’Shaughnessy’spaper,theUSDispensaryclassifiedcannabiscompoundsasuseful
treatmentsforneuralgiaandconvulsivedisorders.By1860theOhioMedicalSocietyCommittee
onCannabisdeclaredefficacyforinfantileconvulsions,epilepsyandmanyotherdisorders.
However,thenarcoticeffectsofcannabisledtounregulatedrecreationaluseandmedicinal
cannabiswascaughtupintheprohibitionmovementthatleadtothebanningofalcoholand
otherdrugs.In1911Massachusettsbecamethefirststatetooutlawcannabis.Otherstates
quicklyfollowedwithmarijuanaprohibitionlawswhichpersistedthroughoutthe20thcentury
suchthatby1970theUSControlledSubstancesActwaspassed,classifyingmarijuanaasadrug
with“noacceptedmedicaluse’.Countriesthroughouttheworldnowhavestringentlawsand
punishmentsforthepossessionanddistributionofcannabis.
BotanicalandchemicalaspectsofCannabisuse
Theherbanditsextractscontainmorethan100chemicallysimilarcompounds(called
cannabinoids).Italsocontainsover400othernon-cannabinoidcompounds.Asweknow,
cannabisremainsbestknownasadrugofrecreationaluseandisconsumedbyapproximately
150millionpeoplearoundtheworldeachday.Recreationaluseimpliestheingestionofleaves,
resinandoilsoftheCannabisSativaplantwhichhaslargeamountsofthepsychoactiveformof
cannabinoidTHC(Tetrahydrocannabadiol).ItiscannabiswhichisrichinTHCthatcausesthe
‘high’peoplecommonlyassociatewiththedrug.However,theIndicaplantproducesamore
fibrouscompoundthathasnopsychoactiveeffectsandthiswasalsoprobablythefirstnon-food
cropgrownbyman(iehemprope,sacksetc).HempisrichinCBD(Cannabadiol)whichisthe
formthatappearstobeusefulfortreatingconvulsivedisorders.WhilethepharmacologyofTHC
isconsideredtobereasonablystraightforward,thepharmacologyofCBDisextremelycomplex;
CBDisamulti-targetdrugwhoseactionisnotcompletelyunderstood.
Overthelast50yearstherehasbeenagrowingcommunityofcampaignersformorewidespread
andregularizeduseofmedicinalcannabis.Amongstthemostpopularindicationsare
chemotherapyinducedanorexiaandchronicpainincancerandmultiplesclerosis.Ofcourse
therehavealsobeenreportsofspectacularreversalsinthetreatmentofepilepsyleadingtoa
chorusofcallsfrompatients,carersandparentsforamorethoroughevaluationofthedrugfor
epilepsy,andifproveduseful,itslegalization.In1996,CaliforniabecamethefirststateintheUS
tolegalizecannabisformedicinaluseonly.Nowcannabisislegalin26statesintheUS.
GrowingEvidencefortheefficacyofCBDinEpilepsy
Thefirstscientificreportsinrecenttimesdidnotappearuntiltheearly2000’s.Afteranumberof
casereportsofsuccessintreatingepilepsy,theissuecametotheforein2013whenDrSanjay
Gupta,CNN’sdoctor,broadcastatwo-partdocumentarycalled“Weed”onmedicinalcannabis
use.TheseriesfeaturesCharlotteFigiayounggirlfromNorthAmericawithDravet’ssyndrome,a
severegeneticformofepilepsythatisoftenresistanttoanti-epilepticdrugsandputssufferersat
riskofsuddenunexpecteddeathinepilepsy(SUDEP).20%ofpeoplewithDravet’swillbedeadby
theageoftwenty.Charlottebegantohaveseizuresattheageof3monthsandby3yearsshe
washavingmorethan300permonth,Shespent3yearsinandoutofintensivecareunits:Her
parentsmovedtoColoradohavingresearchedcannabisandobtainedahighCBDcontentoil
whichhadasuddenanddramaticeffectontheseizures;TheFigi’snotedthattheamountofCBD
ineachpreparationwasimportantandtheyworkedwithalocalgrowerfamily,theStanley
brothers,toperfectthestrainthatworkedbest:TheproducthasbecomeknownasCharlotte’s
Webandthisandotherstorieslikeithaveledtounprecedentedcooperationinopen-labeled
studiesintheU.S.ofEpidiolex(apurifiedphytocannabinoidformofCBDderivedfromthewhole
plantintheUK),whichisproducedbythepharmaceuticalcompanyGWHealth.
Resultsfrom213people(childrenandyoungadults)whoreceivedEpidiolex(99%CBD)inan
openlabelstudywerepresentedfirstattheAmericanAcademyofNeurology,April22,2015The
resultscanbesummarizedasfollows:
•
9%ofpatients(averageage11)becameseizurefree.
•
50%patientssawadecreaseinseizurerateofatleast50%
•
PatientswhohadDravet’sSyndrome(DS)respondedmorepositivelywitha63%decrease
inseizuresover3months.
•
CBDdidnotworkforallandwasassociatedwithadverseeventsincludingdrowsinessin
37%andfatiguein16%.
TwophaseIIIplacebocontrolledstudiesonEpidiolexhaverecentlybeencompleted.Preliminary
resultshavebeenpostedinapressreleasedon26thSeptember2016onGWhealth’swebsite.
https://www.gwpharm.com/about-us/news/gw-pharmaceuticals-announces-second-positivephase-3-pivotal-trial-epidiolex.
Despiteincreasingevidenceinthescientificliteratureofthevalueofthisalmostpureformof
CBD,therearecallsforotherasyetunprovenformstobemadenotonlylegalbutavailablefor
medicinaluse.TheseformshavevariouslevelsofTHCthatadherentsclaimwillimproveitsantiepilepticeffect.Theevidenceforthisisbasedonanecdotalreportsofbenefitinsomechildren.
Whiletheremaybereasonstobeoptimisticthatsuchclaimsmayhavevalidity,thereareasyet
nocontrolledoruncontrolledtrialsbeingruntoendorsesuchaposition.Furthermore,
recreationalformsofcannabiswithhighlevelsofTHChavebeenassociatedwithpsychosisin
susceptiblepopulationsandextremecaution(andsignificantevidence)willberequiredin
determiningthesafelevelofthisdrugtogivetosickchildren.
IssuesfortheavailabilityofCBDinIreland
UnderIrishlaw,cannabisisnotrecognizedashavinganymedicalbenefits.Themostrecent
MisuseofDrugs(Designation)Order(S.I.No.69/1998)listscannabis,cannabisresin,andits
derivativesasschedule1drugsundertheMisuseofDrugsActsof1977,1984to2016.Asa
consequence,manufacture,production,preparation,sale,supply,distributionandpossessionof
cannabisisunlawfulforanypurpose,exceptunderlicensefromtheMinisterofHealthforthe
purposesofresearch.Theavailabilityofvariousformulationsforuseincancer,MSandepilepsy
hasledtocallsforaliberalizationofthelawinrelationtomedicinaluse.Inthelastfewyearsa
formofmedicinalcannabishasbeenspeciallylicensedinIrelandforusetoreducespasticityand
paininMS,calledSativex,butthishasnotbeenreimbursedbygovernmentpaymentschemes
whichmayexplainitsslowuptake.Themainformofcannabisthatappearstoworkforepilepsy
(highCBD,lowTHC)canonlybeconsideredanunscheduleddrugiftheTHClevelisnomorethan
‘trace’.Nevertheless,anumberofformsofhighCBDlowTHCoilscanbepurchasedinretail
storesinIrelandandimportedonline.However,sincethedrugisnotregulatedordesignatedas
amedicinalproductitcannotbeprescribedbyIrishphysicians.
Conclusion
Theuseofcannabistotreatepilepsyoffersatantalizingnewhorizonforseveredisabling
seizures:Thereisanurgencycreatedbythecommunityoffamilieswithsevereepilepsyto
completetheproper,soberandreflectivescientificevaluationoftheefficacyandsafetyofthis
drug.Initialstudiesareencouragingbutnotdefinitive.Already,itispossibletostatewith
confidencethatthisdrugwillnotworkforeveryone,willcauseintolerable,butprobablynot
dangerous,sideeffectsinafew;butforthoseforwhomitwillworkitmaybelife-saving.
DespitetheshorttimescaleforthesehearingsIhavealreadyconsultedwidelywithIrishandUK
colleaguesandinternationalresearchers,includingoneoftheleadresearchersintheUSstudies
quotedabove.Asoflastcountonly10countriesintheworldhavelegalizedcannabisfor
medicinaluseandonlyonecountry(thatIknowof)Australiahasapropernationalframeworkfor
medicinalprescribingforchildrenwithepilepsy.InconjunctionwiththeNationalEpilepsy
ProgrammeandtheIrishsectionoftheInternationalLeagueAgainstEpilepsy(ILAE,president
ProfNormanDelanty,RCSI),withrepresentativesfromRCPIpharmacologyandtherapeutics
committee,weproposetoworkwiththeHPRAtodeterminewhethersuchaframeworkfor
limitedprescribingofpureCBDoilispossiblebasedonthecurrentlevelofevidencewith
particularfocusonthesafetyforchildren.