Cannabinoid Product Board · The creation of the Cannabinoid Product Board and outlines its duties....
Transcript of Cannabinoid Product Board · The creation of the Cannabinoid Product Board and outlines its duties....
CannabinoidProductBoard
AnnualReport
November2017
Prepared by
Cannabinoid Product Board
Chair:KarenWilcoxPh.D.ErikChristensenM.D.
MichaelCrookstonM.D.,F.A.P.A.,F.A.S.A.M.GlenHansonDDS,Ph.D.
MarkMungerPharmD,FCCPEdReddM.D.
PerryRenshawM.D.,Ph.D.,M.B.A
Utah Cannabinoid Product Board
Cannabinoid Product Board Annual Report
Executive Summary November2017
AsmedicalandrecreationalmarijuanabecomeslegalizedacrosstheUnitedStates,theUtahLegislaturehastakenaproactiveapproachandin2017passedTheCannabinoidResearchAct,numberedasHB130.ThisactestablishedtheCannabinoidProductBoardandallowedfortheuseofCannabinoidproductsforresearch.ThepurposeoftheCannabinoidProductBoard(CPB)istoreviewavailableresearchandproviderecommendationstoprescribingphysiciansrelatedtotheuseofcannabinoidproductsfortreatingmedicalconditions,dosageamounts,andidentifyinginteractionswithothertreatments.TheBoardiscomposedofsevenmembers.Medicalresearchers,physicians,andthreeoftheBoardmembersarealsomembersoftheControlledSubstancesAdvisoryCommittee(CSAC).
TheBoardfirstmetinJune2017andbeganholdingmonthlymeetingstoreviewcannabinoidresearch.Annually,theBoardprovidesrecommendationstothelegislatureregardingtheirfindings.ThisreportcontainsthefindingandrecommendationsoftheBoardfromJunetoNovember2017.Below,thereaderwillfindthecriteriamatrixusedforanalyzingresearchaswellasthestudiesthathavebeenreviewedatthispoint.Otheractivitiesoftheboardareexplainedandlimitations,whichwereidentifiedthroughdiscussionandresearchreview,areoutlined.TheBoardhasmaderecommendationsaswellasidentifiednextstepsinthisreport.
KeyPoints:• TheBoardhaslimitedaccesstoinformation,
whichprovesdifficulttomakerecommendationsbasedonpublishedresearchalone.TheBoardwoulddefertorecommendationsfromtheFDA.
• TheBoardrecommendsexpandingthe10:1ratioofcannabidioltoTHCinstatutesothatmorestudiescanbeconsideredforreview.
• TheBoardisunabletorecommendappropriatedosagesortreatmentswithcannabinoidproductswithoutassuranceofqualityandconsistencythroughouttheresearch.
• TheBoardrecommendsthatcannabinoidproductmanufacturersadoptguidelinessimilartothosefromtheAmericanHerbalProductsAssociationforqualitycontrol.
• TheBoardacknowledgesthatthereiscurrentlynotenoughliteraturetomakeconclusionsaboutcannabidioleffectivenessforspecificdiseasestates.
• TheBoardrecommendsreviewingresearchregardingtheharmsassociatedwithcannabinoidproductsinadditiontothebenefitsofsuchproducts.
Utah Cannabinoid Product Board •
TableofContents
Introduction 1
Bylaws...................................................................................................................................2
Website.................................................................................................................................2
Organization 4
ProcessforReviewingandClassifyingResearch...................................................................4
ConclusiveEvidence:.............................................................................................................4
SubstantialEvidence:............................................................................................................5
ModerateEvidence:..............................................................................................................5
LimitedEvidence:..................................................................................................................5
NoorInsufficientEvidencetoSupporttheAssociation:......................................................5
Limitations 11
Scopeoftheboard..............................................................................................................11
Consistencyofproducts......................................................................................................11
Recommendations 13
NextSteps 14
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Introduction
TheCannabinoidProductBoardistheresultoftheCannabinoidResearchAct,sponsoredbyRep.BradDawandSen.EvanVickersduringthe2017GeneralLegislativeSession.TheCannabinoidResearchAct,numberedasHB130,madeseveralchangestothestatecode:
1. Allowtheprocessinganduseofcannabinoidproductsinacademicresearch;
2. Allowthepossessionofcannabinoidproductbysomeoneparticipatinginapprovedresearch;and
3. ThecreationoftheCannabinoidProductBoardandoutlinesitsduties.
TheCannabinoidResearchActreceivedwidesupportinthelegislature.ThebillreceivedunanimoussupportfromtheHouseHealthandHumanServicesCommitteeandreceivedonlytwonayvoteswhenontheHousefloor.IntheSenate,whereHB0130wasintroducedbySen.EvanVickers,theSenateHealthandHumanServicescommitteeapprovedthebill7-1,andpassedtheSenateasawhole27-1-1.Thelegislation,withitsamendments,passedtheconcurrencecalendarunanimously.Gov.HerbertsignedtheCannabinoidResearchActintolawonMarch25th.
TheCannabinoidResearchActdirectstheUtahDepartmentofHealth(UDOH)toformandfacilitatetheCannabinoidProductBoard.Asstatedinthelegislation,thepurposeoftheboardistoreviewavailableresearchrelatedtothehumanuseofcannabinoidproducts.Specificallytheboardisaskedtoevaluatethesafetyandefficacyofcannabinoidproductsintermsof:1)medicalconditionsthatrespondtocannabinoidproducts;2)dosageamountsandtheirmedicalforms;and3)interactionsbetweencannabinoidproductsandothertreatments.TheboardmayonlyreviewresearchthathasbeenapprovedbyanInstitutionalReviewBoard,orapproved/conductedbythefederalgovernment.
Fromthisresearch,theboardhasbeenaskedtodevelopprescribingguidelinesthatmaypotentiallybeusedbyphysiciansrecommendingcannabinoidproductstotheirpatients.TheboardisdirectedtoreportthefindingsoftheirevaluationinwritingtotheHealthandHumanServicesInterimCommitteebeforeNovember1stofeachyear.
ThelegislationoutlinesthattheCannabinoidProductBoardbemadeofthesevenmembers“…inconsultationwithaprofessionalassociationbasedinthestatethatrepresentsphysicians.”Threeoftheboardmembersmustbemedicalresearchersandfourmustbephysicians.ThreeoftheboardmembersmustalsobemembersoftheControlledSubstancesAdvisoryCommittee(CSAC).Thetermsofboardmembers,leadership,andvotingonrecommendationsarealsodiscussed.
TheExecutiveDirectorsOffice(EDO)ofUDOHbegantheprocessofidentifyingpotentialboardmembersandissuingappointmentsinApril,2017.
Thoseappointedinclude:
ErikChristensenM.D.* UtahDepartmentofHealthOfficeofMedicalExaminer
MichaelCrookstonM.D.,F.A.P.A.,F.A.S.A.M.
IntermountainMedicalGroup
GlenHansonDDS,Ph.D.*
UniversityofUtah,HealthSciencesCenter
MarkMungerPharm.D.*,F.C.C.P.,F.A.C.C.,F.H.F.S.A.
UniversityofUtah,HealthSciencesCenter
EdReddM.D. UtahLegislatorPerryRenshawM.D.,Ph.D.,M.B.A
UniversityofUtah,HealthSciencesCenter
KarenWilcoxPh.D. UniversityofUtah,HealthSciencesCenter
*CSACMembers
FacilitationoftheCannabinoidProductBoardwasdelegatedtotheTobaccoPreventionandControlProgramwithintheBureauofHealthPromotion.
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Bylaws
TheCannabinoidProductBoardadoptedbylawstodefinethestructureoftheBoardandtohelpguidetheBoardsdecisionsandoperations.ThebylawswereadaptedfromtheColoradoMedicalMarijuanaScientificAdvisoryCouncilbylawswithinclusionofrequirementsinH.B.130.Thebylawscontainthedutiesoftheboard,whicharedefinedas:
ARTICLEIV:DutiesoftheBoardSection1.TheBoardshall:1)Reviewanyavailableresearchrelatedtothehumanuseofacannabinoidproductthat:
a) wasconductedunderastudyapprovedbyanIRB,or
b) wasconductedorapprovedbythefederalgovernment
2)Basedontheresearch,theBoardshallevaluatethesafetyandefficacyofcannabinoidproducts,including:
a) medicalconditionsthatrespondtocannabinoidproducts
b) cannabinoiddosageamountsandmedicaldosageforms;and
c) interactionofcannabinoidproductswithothertreatments
3)BasedontheBoard’sevaluation,theBoardshalldevelopguidelinesforaphysicianrecommendingtreatmentwithacannabinoidproductthatincludesalistofmedicalconditions,ifany,thattheBoarddeterminesareappropriatefortreatmentwithacannabinoidproduct.
4)TheBoardshallsubmittheguidelinesto:a) thedirectoroftheDivisionofOccupationaland
ProfessionalLicensingb) theHealthandHumanservicesInterim
Committee5)TheBoardshallreporttheBoard’sfindingsbeforeNovember1ofeachyeartotheHealthandHumanServicesInterimCommittee.ThebylawscontaininformationregardingtheresponsibilitiesoftheDepartmentofHealthandhowmeetingsshouldbeconductedusingRobert’sRulesofOrder,aswellashowtodealwithconflictsofinterest.
Website
TheCannabinoidsProductBoarddevelopedafreepublicwebsiteforthepurposeoforganizingresearch,providingaplaceforpubliccommentandaddinganextralayeroftransparencytotheproceedingsoftheboard.Thewebsitecanbefoundat:https://sites.google.com/utah.gov/cpboard/.ThewebsitecontainsinformationofwhenandwheretheBoardmeetingswillbeheld,upcomingandpastagendas,andmeetingminutesforallCPBmeetings.Thewebsitealsocontainsasectionforresearch,whichhascopiesofalltheliteraturethatisbeingreviewedbytheboard.ThiswebsiteisalsoaplaceforthepublictointeractwiththeBoard.ThepubliccansubmitcommentsorquestionstotheBoard,whichtheBoardwillhavetheopportunitytorespondto.
*BelowarescreenshotsoftheUtahCannabinoidProductBoardWebsite
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OrganizationIntheinitialmeetingoftheCannabinoidProductBoard,theBoardvotedonselectingachairperson.KarenWilcox,Ph.D.whoisaprofessorandchairoftheDepartmentofPharmacology&ToxicologyattheUniversityofUtahwasselectedtobethechair.TheBoarddoesnothaveaco-chair,thoughthebylawsallowforoneifneededinthefuture.TheBoardhasdecidedtomeetmonthlyandwillcontinuetodosoasneeded.Thusfarfourboardmeetingshavebeenheld.Theagendaofatypicalboardmeetingconsistsofadministrativeitemssuchasapprovingthepreviousmeetingminutes,andreviewofpublishedresearch.Theresearcharticlesareassignedtomembersoftheboardtoreadandthentheyreportontheresearchatthemeeting.Afterpresentingtheresearch,eacharticleisdiscussedbytheBoard,andplacedintotheestablishedmatrixforscoring.TheresearchthatisreviewedisidentifiedprimarilybytheBoardinternbasedonthecriteriaforstudiesoutlinedinHB130.MembersoftheBoardalsobringrelevantresearchforwardfordiscussion.TheBoardisinterestedinhavingsubjectmatterexpertssuchasresearchersandpharmacologicalorganizationspresenttotheBoardandprovidefurtherinformationaboveandbeyondwhatresearchcanprovide.
ProcessforReviewingandClassifyingResearchTheCannabinoidProductBoardhasbeenaskedtoevaluatethesafetyandefficacyofcannabinoidproductsintermsof:1)medicalconditionsthatrespondtocannabinoidproducts;2)dosageamountsandtheirmedicalforms;and3)interactionsbetweencannabinoidproductsandothertreatments.AssuchtheBoardneededtocreateprocessesbywhichtheycouldsystematicallyreviewtheevidencewhichmetthecriteriaoutlinedinthestatue.TheBoardagreeduponusingthecategoriesusedbytheInstitutesofMedicinetocategorizeevidenceittheirbook“TheHealthEffectsofCannabisandCannabinoids:TheCurrentStateofEvidenceandRecommendationsforResearch”,toclassifystudyrecommendationsaswellastodeterminethelevelofevidenceforeachstudyreviewed.Itwasdecidedthatallresearchreviewedwouldbeputintoa
matrixthatidentifiesthespecificdiseasestateortopicthestudylookedat,studymethods(typeofstudy,samplesize,location),keyfindings,keylimitations,adeterminationofthelevelofevidenceaswellasagradingorclassificationoftherecommendations.Pleaseseeexamplebelow.UsingthismatrixasaguidetheBoardwouldsystematicallyworkthroughgradingeachpieceofevidence.TheBoardalsoinvitedrepresentativesfromvarioussuppliersofhighquality,pharmacygrade,cannabidialproductstopresenttotheBoardtogainabetterunderstandingoftheresearchbeingconductedandtheproductscurrentlyonthemarket.TheBoardadoptedstandardlanguagedevelopedbytheInstitutesofMedicinetocategorizetheweightofevidenceregardingwhethercannabinoiduseisaneffectiveorineffectivetreatmentforthespecifiedcondition.TheCategoriesandthegeneralparametersforthetypesofevidencesupportingeachcategoryarelistedbelow.1Theevidencecategoriessuggestthatthestudydesignwasappropriateforthelimitedconclusionsreachablebasedonthelimitationsinthedata.ItdoesnotindicatethattheBoardagreesordisagreeswithanyconclusionorrecommendation.
ConclusiveEvidence:Fortherapeuticeffects:Thereisstrongevidencefromrandomizedcontrolledtrialstosupporttheconclusionthatcannabinoidsareaneffectiveorineffectivetreatmentforthehealthendpointofinterest.Forotherhealtheffects:Thereisstrongevidencefromrandomizedcontrolledtrialstosupportorrefuteastatisticalassociationbetweencannabinoiduseandthehealthendpointofinterest.Forthislevelofevidence,therearemanysupportivefindingsfromgood-qualitystudieswithnocredibleopposingfindings.Afirmconclusioncanbemade,andthelimitationstotheevidence,includingchance,bias,andconfoundingfactors,canberuledoutwithreasonableconfidence.
1National Academies of Sciences, Engineering, and Medicine. 2017. Thehealtheffectsofcannabisandcannabinoids:Thecurrentstateofevidenceandrecommendationsforresearch.Washington, DC: The National Academies Press. doi: 10.17226/24625.
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SubstantialEvidence:Fortherapeuticeffects:ThereisstrongevidencetosupporttheconclusionthatcannabinoidsareaneffectiveorineffectivetreatmentforthehealthendpointofinterestForotherhealtheffects:Thereisstrongevidencetosupportorrefuteastatisticalassociationbetweencannabinoiduseandthehealthendpointofinterest.Forthislevelofevidence,thereareseveralsupportivefindingsfromgood-qualitystudieswithveryfewornocredibleopposingfindings.Afirmconclusioncanbemade,butminorlimitations,includingchance,bias,andconfoundingfactors,cannotberuledoutwithreasonableconfidence.
ModerateEvidence:Fortherapeuticeffects:Thereissomeevidencetosupporttheconclusionthatcannabinoidsareaneffectiveorineffectivetreatmentforthehealthendpointofinterest.Forotherhealtheffects:Thereissomeevidencetosupportorrefuteastatisticalassociationbetweencannabinoiduseandthehealthendpointofinterest.Forthislevelofevidence,thereareseveralsupportivefindingsfromgood-tofair-qualitystudieswithveryfewornocredibleopposingfindings.Ageneralconclusioncanbemade,butlimitations,includingchance,bias,andconfoundingfactors,cannotberuledoutwithreasonableconfidence.
LimitedEvidence:Fortherapeuticeffects:Thereisweakevidencetosupporttheconclusionthatcannabinoidsareaneffectiveorineffectivetreatmentforthehealthendpointofinterest.Forotherhealtheffects:Thereisweakevidencetosupportorrefuteastatisticalassociationbetweencannabinoiduseandthehealthendpointofinterest.Forthislevelofevidence,therearesupportivefindingsfromfair-qualitystudiesormixedfindingswithmostfavoringoneconclusion.Aconclusioncanbemade,butthereissignificantuncertaintyduetochance,bias,andconfoundingfactors.
NoorInsufficientEvidencetoSupporttheAssociation:Fortherapeuticeffects:Thereisnoorinsufficientevidencetosupporttheconclusionthatcannabinoidsareaneffectiveorineffectivetreatmentforthehealthendpointofinterest.Forotherhealtheffects:Thereisnoorinsufficientevidencetosupportorrefuteastatisticalassociationbetweencannabinoiduseandthehealthendpointofinterest.Forthislevelofevidence,therearemixedfindings,asinglepoorstudy,orhealthendpointhasnotbeenstudiedatall.Noconclusioncanbemadebecauseofsubstantialuncertaintyduetochance,bias,andconfoundingfactors.
ResearchReview:
TheresearchlistedinthematrixbelowwascompiledbytheCPBinternandreviewedbytheBoard.Theresearchpresentedwasidentifiedbyhavinga10:1ratioofcannabidioltoTHC.Thisratiolimitsthenumberofstudiesthatcanbereviewed,butthereviewprocessisongoingasstudiesthatmeetthiscriterionareidentified.
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TitleandAuthors Journal,Year(reference)
Methods(Typeofstudy,samplesize,study,location,etc.)
WeightofEvidenceCategory
KeyFindings KeyLimitations Comments(Industryties,etc.)
“TrialofCannabidiolforDrug-ResistantSeizureintheDravetSyndrome”,Devinsky,etal
NEnglJMed2017;376:2011-20.
DOI:10.1056/NEJMoa1611618
RandomizedControlledTrial;Double-blind,placebocontrolled
N=120
14-weektreatmentperiod
Dosagesof20mgperkgofbodyweightperdayofcannabidioloralsolutionorplaceboinadditiontostandardantiepileptictreatment.
Multinational:23centersintheU.S.andEurope
Sample:Children/youngadults(2-18yearsold)withtheDravetsyndrome(Epilepsydisorderassociatedwithdrug-resistantseizuresandhighmortalityrate)
Meanage:9.8yearsold
52%male
90%completedthetreatmentperiod
Conclusiveevidence
Cannabidiolresultedinagreaterreductioninconvulsive-seizurefrequencythanplaceboamongchildrenw/drug-resistanceDravetsyndrome.Cannabidiolgroup:-Decreaseinmedianfrequencyinconvulsiveseizurespermonthfrom12.4to5.9.-Percentageofpatientsw/atleasta50%reductioninconvulsive-seizurefrequency:43%.-5%becameseizurefree-Nosignificantreductioninnonconvulsiveseizures.-Adverseevents:diarrhea,vomiting,fatigue,pyrexia,somnolence,abnormalliver-functiontestresults.-Overallconditionimprovedbyatleastonecategoryonthe7-categoryCaregiverGlobalImpressionofChangeScale:62%Controlgroup:
Dataonconvulsiveseizures(numberandtype)wasrecordedeachdaybypatientsortheircaregivers.
ResultsofCaregiverGlobalImpressionofChangeareself-reportedona7-pointLikert-likescale.
Funded,designed,managed,monitored,andanalyzedbyGWPharmaceuticals
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-Decreaseinmedianfrequencyofseizurespermonthfrom14.9to14.1.-Percentageofpatientsw/atleasta50%reductioninconvulsive-seizurefrequency:27%.-Lessadverseeventsoccurred-0%becameseizurefree-Overallconditionimprovedbyatleastonecategoryonthe7-categoryCaregiverGlobalImpressionofChangeScale:34%Mediandifferencebetweencannabidiolgroupandplacebogroupinseizurefrequency:-22.8percentagepoints;95%CI,-41.1to-5.4;P=0.01
“Cannabidiolenhancesanandamidesignalingand
alleviatespsychoticsymptomsofschizophrenia”,Leweke,etal
TranslPsychiatry(2012)2,e94,doi:10.1038/tp.2012.15&2012MacmillanPublishersLimitedAllrightsreserved2158-3188/12
RandomizedClinicalTrial;therapeutic-exploratory(phaseII);Double-blind:cannabidiolvsamisulpride(apotentantipsychotic).
N=42
Sample:Age18-50yearsold;maleandfemale;alldiagnosedwithparanoidschizophrenia
Conclusiveevidence
Boththecannabidioltreatmentandamisulprideweresafeandequallyeffectiveatimprovingpsychoticsymptoms.
Cannabidioltreatment:-Superiorside-effectprofile:lessweightgainandlowerprolactinincrease-apredictorofgalactorrheaandsexual
Theprimarypharmacologicalmechanismthroughwhichcannabidiolexertsanipsychoticeffectsinnotyetclear.Thestudycouldnotexcludethatcannabidiolmayreducepsychoticsymptomsthroughcomplementaryor
ThestudywassupportedbygrantsfromtheStanleyMedicalResearchInstitute(FML)andtheNationalInstituteonDrugAbuse(DP).
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Location:DepartmentofPsychiatryandPsychotherapyoftheUniversityofCologne
Allpatientswerehospitalizedatbaselineandthroughday28afterrandomassignmenttotreatment.
Afterascreeningperiodofupto7daysandaminimumperiodof3antipsychotic-freedays,patientswererandomized(1:1)toreceiveeithercannabidioloramisulpridestartingwith200mgperdayeachandincreasedstepwiseby200mgperdaytoadailydoseof200mgfourtimesdaily(total800mgperday)eachwithinthefirstweek.Treatmentsweremaintainedforanother3weeks.
dysfunction.Well-tolerated-Significantincreaseinserumanandamidelevels,whichwassignificantlyassociatedwithclinicalimprovement.
evenalternativemechanismstoFAAHinhibition,includinginteractionswithserotonin5-HT1Areceptors,GPR55receptorsandtransientreceptorpotentialvanilloid-1receptors.TheresultsprovidearationaleforadditionalclinicaltestingofselectiveFAAHinhibitorsinschizophrenia.
“Safetyandpharmacokineticsoforalcannabidiolwhenadministeredconcomitantlywithintravenousfentanylinhumans”,Maninietal
JAddictMed.2015May-Jun;9(3):204–210.
doi:10.1097/ADM.0000000000000118
Double-blind,placebo-controlledcross-overstudyN=34(eachsubjecthadtwosessions;n=17)Sample:21-65yearsold;healthyvolunteerswithprioropioidexposure,regardlessofroute.Location:ClinicalResearchCenterinMountSinaiHospital
Moderateevidence
Cannabidioldoesnotexacerbateadverseeffectsassociatedwithintravenousfentanyladministration.Co-administrationofCBDandopioidswassafeandwelltolerated.Importantly,
Subjecttopotentialselectionbiasduetonotincludingparticipantsacrossallages,gender,andethnicbackgrounds.Self-reportingcouldhaveledtobias,but
ThestudywasfundedbyaresearchgrantfromtheNationalInstitutesofHealth.
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inNewYorkCityCannabidiol(CBD)wasorallyco-administeredwithintravenousfentanyl.Participantsadministeredeitherplacebo,400mgoralCBD,or800mgoralCBD.2sessions:Session1:.5mcg/Kg;Session2:1.0mcg/KgofIVfentanyl.Bloodsampleswereobtainedbeforeandafter400or800mgCBDpretreatment,followedbyasingle0.5(Session1)or1.0mcg/Kg(Session2)intravenousfentanyldose.Primaryoutcome:SystematicAssessmentforTreatmentEmergentEvents(SAFTEE)toassesssafetyandadverseeffects.Alsomeasured:CBDpeakplasmaconcentrations,timetoreachpeakplasmaconcentrationsandareaunderthecurve.
fentanylco-administrationdidnotproducerespiratorydepressionorcardiovascularcomplications.
thestudydidutilizeacombinationofself-reportingandobjectivemeasures(vitalsigns,urinetesting,bloodsampling).Participantswereexcludediftheyhadacurrentdiagnosisofdrugdependence(exceptnicotine)orapositivedrugscreen.
Thestudynotedthatit’spredictedthatCBDwouldhaveasignificanteffectoninhibitingheroin-seekingbehavior,butthattherearestilllargegapsofknowledgeaboutCBDactionsinthebrain.
“Low-DoseCannabidiolIsSafebutNotEffectiveintheTreatment
forCrohn’s
DigDisSci(2017)62:1615–1620
DOI10.1007/s10620-017-4540-z
RandomizedControlledTrial;placebo-controlled
N=19
Sample:18-75yearsoldwithaCrohn’sdiseaseactivityindex
InsufficientEvidencetoSupporttheAssociation
(small
CBDwasfoundtobesafetoadministertoCrohn’spatients,butdisplayednobeneficialeffects.
TheaverageCDAIbeforecannabidiolconsumptionwas337±108and308±
SmalldoseofCBDwasused.
Smallnumberofpatientsinthestudy.
Dosagewasgivenorally,whichmaybe
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Disease,aRandomizedControlledTrial”,Naftalietal.,
>200.11weremales.
Patientswererandomizedtoreceive10mgofcannabidiol(CBD)orallyorplacebotwicedaily.
samplesizeandsmalldosages)
96(p=NS)intheCBDandplacebogroups,respectively.After8weeksoftreatment,theindexwas220±122and216±121intheCBDandplacebogroups,respectively(p=NS).Hemoglobin,albumin,andkidneyandliverfunctiontestsremainedunchanged.Nosideeffectswereobserved.
lesseffectivethansmoking.
6patientsinthestudygroupwerecurrentsmokers,butnoneintheplacebogroupwere.SmokingisknowntobeharmfulinCrohn’sdisease.
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Limitations
Scopeoftheboard
UtahCode§26-61-202statesthatthepurposeoftheCannabinoidProductBoard(theBoard)istoreviewavailableresearchto“…evaluatethesafetyandefficacyofcannabinoidproducts…”IntheCannabinoidResearchActtheterm“cannabinoidproduct”isdefinedas:
“…aproductintendedforhumaningestionthat:
(i)containsanextractorconcentratethatis obtainedfromcannabis;
(iii)ispreparedinmedicinaldosageform;and
(iii)containsatleast10unitsofcannabidiolfor everyoneunitoftetrahydrocannabinol.”(UC§ 58-37-3.6(1)(a))
TheBoard,uponbeginningtoidentifyresearchtoreview,discoveredthattherearefewpublicallyavailableresearcharticleswhereintheadministeredproductmetthedefinitionof“cannabinoidproduct”asdefinedinstatecode.
Thelackofavailableresearchpreventstheboardfromconfidentlyfulfillingitspurposeofevaluatingsafetyandefficacyoftheseproducts.
Consistencyofproducts
ThepurposeoftheCannabinoidProductBoardinevaluatingthesafetyandefficacyofcannabinoidproductsissimilartothemissionoftheUnitedStatesFoodandDrugAdministration(FDA)insomuchthattheFDAseekstoensurethesafety,efficacy,andsecurityofdrugs,biologicalproducts,andmedicaldevicestoprotectthepublic.Toachieveitspurpose,theFDAhasputintoplaceregulationsforproductsdefinedaspharmaceuticals,botanicaldrugs,ordietarysupplements.Suchregulationsareknownbroadlyas
Chemistry,Manufacturing,&Controls(CMC)andCurrentGoodManufacturingPractices(cGMP).
DuringtheresearchanddevelopmentstageofanewpharmaceuticaltheFDArequirescompaniestocomplywithCMCguidancetobegrantedapproval.CMCsinvolvedocumentationof:
- Drugcomposition;- Manufacture;- Stabilityoftheactivesubstance;- Formulationoffinalproduct;- Appropriatevariationlimits;- Releasecriteria(qualitystandardsforwhenthe
drugcanbemadeavailable);and- Theresultsofanalyticaltesting.
Whenthepharmaceuticalbeingassessedisbotanicalinnatureandthushasmultiplecomponentsinthesameproduct,therequirementsofCMCschangeandalsoinclude:
- Authenticationofplantsource- Recordofplantspecimens- Historyofthelandusedtogrowtheplant
source- Awrittenandapprovedprocessofthegrowing
processincludingtheusechemicalsontheplantsource.
- Packaging- Andspecificationsoftheallowablelimitsof
potentiallyharmfulcontaminants.
WiththisinformationtheFDAcanassessanddecidewhethertheproducingcompanycanadequatelyandconsistentlyproduceawell-definedproductatahighstandard.
TheneedofCMCsisdifferentbasedontheintentoftheproduct.CMCsareneededforproductsthatareintendedforhumanusetotreatdisease(pharmaceuticals).Physiciansareinvolvedwiththeuse
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ofpharmaceuticalsandwhereinthephysicianprescribestheiruseanddose.CMCsarenotneededforproductsthatareinsteadintendedtosupplementdiettosupporthealth(dietarysupplements).Dietarysupplementsdonotrequireaphysician’sprescription.AsdietarysupplementsarenotintendedtobeusedtotreataspecificdiseasethestandardfortheirdevelopmentislessregulatedbytheFDAandiscomparabletotherequirementsoffoodproducts.
CurrentGoodManufacturingPracticesarethoseregulationsenforcedbytheFDAonceapharmaceuticalisonthemarkettoensurethatcompaniesproducesafe,consistent,andeffectiveproducts.Manyoftheseregulationsarefocusedonfacilitieswheremanufacturingandprocessingofpharmaceuticalsoccurtoensurethattheyareproperlydesigned,monitored,andcontrolled.Specifically,cGMPsrequire:
- Qualitymanagementsystem;- Useofhigh-qualityrawmaterials;- Operatingprocedures;- Qualitymonitoringandinvestigation;- Laboratorytesting;and- FDAinspections
cGMPsarerequiredforbothpharmaceuticalsanddietarysupplements.However,inthecaseofdietarysupplements,manufacturersareallowedtosettheirowncGMPspecificationswithoutFDAapprovalorauditing.Also,unlikeintheproductionofpharmaceuticalsthefacilitieswheredietarysupplementsareproducedneednotbelicensedbytheFDA.
AscannabinoidproductsareneitherpharmaceuticalsnordietarysupplementstherearenoCMCsorcGMPsfortheirdevelopmentorproductionfromtheFDA.ForthosestatesthathaveinstitutedasystemofmedicalcannabistherearesomevaryingrequirementstotryandpromotequalityhoweversuchregulationsdonotmeetthestandardsofCMCsorcGMPs.
Thelackofregulatorystandardsforcannabinoidproductsisimportantforseveralreasons.First,therearenoadequatecontrolstopreventthepresenceofharmfulproductconstituentsthatmayhavebeenintroducedtotheproducteitherthroughthegrowing,processing,ormanufacturingstages.Assuchitisdifficulttoevaluateaproductforside-effectsandinteractionswithothertreatments.Thisraisesethicalissuesiftheseproductsarerecommendedtotreatvulnerableindividuals.
Second,withoutCMCsorcGMPsitisdifficulttoensuretheconsistencyoftheend-product.Inconsistentproductmakesitdifficulttoevaluatetheefficacyofatreatment.Variationinthepotencyofactiveingredientsandotherproductcomponentsmeantryingtolinktheuseoftheproducttohealthbenefitsisnearimpossible.Likewise,whenphysiciansrecommendsuchproductstopatients,physicianswouldbeunabletorecommenddosageaseachbatchofthatproductmaydifferfromthelast.
ItistheopinionoftheBoardthatthelackofregulationoncannabinoidproductsraisesseriousquestionsregardingtheirqualityandreproducibilityintheacademicliteratureavailable.Withouttheassuranceofqualityandconsistency,theboardisunabletorecommenddiseasestateswhereincannabinoidproductscouldbeusedtotreat,orrecommendappropriatedosing.
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Recommendations
• TheBoardhashaveverylimitedaccesstotheinformationnecessarytomakerecommendationsregardingconditionsthatrespondtocannabinoidproducts,prescribingguidelines,anddruginteractions.Anexampleisthatsomeresearchstudiesdonotspecifyhowthecannabinoidproductwasprepared,orthereasoningbehindwhycertaindosageswereused.Alternatively,theFDAhasaccesstoamuchlargerbodyofinformationandanestablishedprocess,whichwouldmaketheirrecommendationsmoreaccurateandappropriate.Duetothisfact,theBoardwoulddefertorecommendationsfromtheFDA.
• ThescopeofwhattheBoardcanreviewasoutlinedinthestatuteisverynarrowandestablisheslimitstothe
cannabinoidproductsthatcanbetakenintoconsideration.Currently,a10:1ratioofcannabidioltoTHCiswhatisallowedinstatute.Whileconductingliteraturereviews,itisclearthattherearenotmanystudiesthatmeetthesecriteria.ThisseverelylimitsthenumberofstudiestheBoardcanreviewandtakeintoconsideration.TheBoardrecommendsexpandingtheratiobeyondthecurrentlimitationofa10:1ratioofcannabidioltoTHC.
• WhiletheBoardhasbeenmainlyfocusingonthepotentialbenefitsofcannabidiol,theBoardrecommendsalso
lookingintotheharmsassociatedwithcannabinoidproductsasthosefindingswillalsobeimportantforphysiciansprescribingtheseproducts.
• AstheBoardfocussesonspecificdiseasesforliteraturereview,itbecomesapparentthatinmostcasesthereis
notliteratureornotenoughliteraturetomakeconclusionsaboutcannabidioleffectiveness.TheBoardhighlyrecommendsnotmakingconclusionsbasedonasingleorveryfewstudies.
• ItistheopinionoftheBoardthatthelackofregulationorChemistry,Manufacturing,&Controls(CMC)and
CurrentGoodManufacturingPractices(cGMP)oncannabinoidproductsraisesseriousquestionsregardingtheirqualityandreproducibilityintheacademicliteratureavailable.Withouttheassuranceofqualityandconsistency,theboardisunabletorecommenddiseasestateswhereincannabinoidproductscouldbeusedtotreat,orrecommendappropriatedosing.
• TheBoardrecommendsthatcannabinoidproductmanufacturersadoptguidelinessimilartothosefromthe
AmericanHerbalProductsAssociationforcultivationandprocessing,manufacturingandrelatedoperations,laboratorypractice,anddispensingsothatresearchanddiseaseinteractionsareconsistent.
Utah Cannabinoid Product Board Page 14 of 14
NextSteps
• TheBoardwillcontinuetomeetmonthlyorasnecessarytoreviewresearcharticlesandutilizetheresearchmatrixtoclassifycannabinoidstudiesthatshowpromiseorharmforprescribingpurposes.
• Inadditiontoresearch,theBoardwillbringinexpertsfromavarietyofbackgroundstofurtheradvancethe
Board’sknowledgeofcannabinoidproductsandresearch.
• TheBoardhashiredanintern,Ms.KrisanaFinlay,whoisastudentattheUniversityofUtah,studyingpublicpolicyandpublichealth.Ms.Finlaywillassisttheboardinfindingandcompilingresearch,draftingreports,andassistingtheBoardwithvariousdutiesasassigned.