Cannabinoid Product Board · The creation of the Cannabinoid Product Board and outlines its duties. The Cannabinoid Research Act received wide support in the legislature. The bill

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

Utah Cannabinoid Product Board Page 1 of 14

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.


EdReddM.D. UtahLegislatorPerryRenshawM.D.,Ph.D.,M.B.A


KarenWilcoxPh.D. UniversityofUtah,HealthSciencesCenter

*CSACMembers

FacilitationoftheCannabinoidProductBoardwasdelegatedtotheTobaccoPreventionandControlProgramwithintheBureauofHealthPromotion.


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



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.


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.


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


-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).


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.


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


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.


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


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.


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.


NextSteps

• TheBoardwillcontinuetomeetmonthlyorasnecessarytoreviewresearcharticlesandutilizetheresearchmatrixtoclassifycannabinoidstudiesthatshowpromiseorharmforprescribingpurposes.

• Inadditiontoresearch,theBoardwillbringinexpertsfromavarietyofbackgroundstofurtheradvancethe

Board’sknowledgeofcannabinoidproductsandresearch.

• TheBoardhashiredanintern,Ms.KrisanaFinlay,whoisastudentattheUniversityofUtah,studyingpublicpolicyandpublichealth.Ms.Finlaywillassisttheboardinfindingandcompilingresearch,draftingreports,andassistingtheBoardwithvariousdutiesasassigned.

Documents

Cannabinoid Product Board · The creation of the Cannabinoid Product Board and outlines its duties. The Cannabinoid Research Act received wide support in the legislature. The bill