Cannabis: taste and flavor - MASCC · Flavor: taste, smell, texture, temperature, vision Causes of...
Transcript of Cannabis: taste and flavor - MASCC · Flavor: taste, smell, texture, temperature, vision Causes of...
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Cannabis:tasteandflavor
JoelB.EpsteinDMD,MSD,FRCD(C),FDSRCS(E),Dipl.ABOMProfessorandDirectorCancerDen?stry,Cedars-SinaiHealthSystemandMedicalDirector,DentalOncology,CityofHopeNa?onalMedicalCenter
LosAngeles,CA
Inorelateddisclosures
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Flavor: taste, smell, texture, temperature, vision Causes of Taste Change in Cancer Survivors: • Cancer Therapy:
� Surgery � Radiation � Chemotherapy � Targeted therapies � Immunotherapy
• Supportive care/ analgesics/other medications • Comorbidities • Oral conditions Underreported; Understudied; Impactful
TasteChangeinCancerSurvivors
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DoctorsvPa3entSymptomReportinBCChemotherapy
Physicianevalua3on(CTCAE) Pa3entReport
Bayo J, Prieto B, Rivers J. The Breast J 2015
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A 10-item, CTCAE derived questionnaire was administered to 600 breast cancer pts in adj chemo. Comparison of physician and pt reports.
JAMA Oncology 2016
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BurdenofTasteandSmellchanges
Oral hygiene Dental health Oral habits
TASTE CHANGE
immunosuppression
Malnourishment
food avoidance Diet change
↓perfomance status
ModifyCAtreatment
Cancer Cancer TX
Hyposalivation Mucositis
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� Limited studies (!) � Most data in breast cancer (taste changes,
metallic dysgeusia, preference for sweet) � ↑ incidence with docetaxel (possible
symptom cluster with CIPN?) � Impact on fatigue and quality of life! � Persistance of the symptom after treatment
CHEMOTHERAPY-INDUCEDTASTE&SMELLChanges
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TASTEANDSMELLAFTERHSCT
OkadaN,etal.SupCareCancer2016;24:3979-85
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� Variableincidence:àima?nib13-40%àsorafenib15-30%àsuni?nib10-60%àeverolimus/temsirolimus10-20%àlapa?nib10%àvismodegib50-70%
TARGETEDTHERAPY:TASTEANDSMELLChanges
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Tastefunc3onfollowingHNC:qualita3veresearch• “Ea?ngismorethannutri?on…it’salsoaverypleasurable
experience….mydaughtersareboth,Iguessyouwouldcall“foodies”…itislikeanac?vityforusmorethanjustea?ngfoodfornutri?on,it’ssomethingthatwedoforfun.Weenjoyea?nggoodfoods.”(GS=1.54)
• “Havinggonethroughacoupleofmonthsofonlydrinkingliquids…itmeansalot.Iliketoeat.”(GS=0.15)
• “BeforecancerIatetolive,andnowIlivetoeat…IneverreallyappreciatedfoodinthewaythatIdonowthatIcaneatagain.It’sagijIappreciatealotmore.”(GS=0.21)
• “Thetasteoffoodisofsignificantimportance…it’salmostuptherewithsexintermsofyouknow,whatitbringsfromalistofthingsyoucouldn’tlivewithout…”(GS=0.02)
• GanzerH,etal.OralOncol2015
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Taste
Evaluatecontentoffood&preventinges?onoftoxicsubstances• Biner:detectssubmicromolarlevelsoftoxic/noxious
compounds• Sour:warnsofnoxious/poisonousagents• Sweet:iden?fiesenergy-richnutrients• Salt:ensuresintakeforelectrolytebalance• Umami:(savory/pleasure)
– recognizesaminoacids(glutamate,aspartate);MSG
Chandrashekaretal,Nature2006444:288-94
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Gusta3onSpecialisedepithelialcells:TongueSojpalatePharynxLarynxUpper1/3ofoesophagus
Eachtastebud:50-100taste-receptor
cells;lifespanof~10-14daysNosegrega?onoftastequali?esinthe
humantongueScon,CurrOpinNeurobiol200414:423-7Scon,Neuron200548:455-64Chandrashekaretal,Nature2006444:288-94
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Gusta3on–sugar/aminoacidreceptorsSweetandaminoacids–determinedbyT1Rgenes(T1R1,T1R2&
T1R3)• T1Rreceptorsfunc?onasdimers
• T1R1+3–aminoacids(MSG&aspartate;“umami”)
• T1R2+3–sugars(includingsaccharin)Func?onasGproteincoupledreceptors(GCPCR)Tunedtoindividualcompounds(siteofligandbindingdeterminesrecogni?onofquality)KnockoutofT1R2+T1R3causeslossofsweetSweetpreferencedeterminedbyT1R
Scon,CurrOpinNeurobiol200414:423-7Scon,Neuron200548:455-64Chandrashekaretal,Nature2006444:288-94
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Gusta3on–biTerreceptors
BiTer–determinedbyT2Rgenes(~25)DifferentT2Rreceptorsrecognise
differentcompoundse.g.hT2R14–picrotoxininhT2R28–phenylthiocarbamideMostT2RsexpressedonthesameTCR-
thecellsarebroadlytunedhighaffinitybinerreceptorsonasinglecell
Scon,CurrOpinNeurobiol200414:423-7Scon,Neuron200548:455-64Chandrashekaretal,Nature2006444:288-94
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Taste–saltandsourSalt: sodiumchannels?(receptorunknown)Sour: Acidsensingprotonchannels?
Calciumchannels? Chloridechannels? Potassiumchannels? PKD2L1(involved)
Vhandrashekaretal,Nature2006444:288-94
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Umami
• Savory,desirable,enjoyable,goodtaste• intensifiesothertastesensa?ons• Aminoacidrichfoods,freeglutamate• Glutamatereceptors:
– T1R1/T1R3;mGluR4,mGluR1
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FreeFaTyAcidReceptors(FFAR)• Fanytaste:roleenergyintake&taste/texturepreferences• Role:energyintake&appe?teviasecre?onofinsulin&incre?n&
sympathe?cs?mula?on• HaraT,KimuraIetal.RevPhysiolBiochemPharmacol2013;Apr30
• FFAR:G-proteincoupledreceptors(GPCR)oralcavity&GIT• Medium&longchainFFARGPR40(Ffar1)&GPR120;ontastebud
typeI,IIcells• Animalstudy:FA:tes?nglinoleicacid&oleicacid• FFAalsomodifybinertaste,butnotmediatedbyGPR40/120
• CartoniCYasumatsuK,OhkuriTetal.JNeurosci2010;30:8376-82
SpicyTaste• C-fibers/Aẟfibers/neuropathy
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Tastesignaling&Neuropep3deSecre3on• Sweet,biner,umami↑calciumhomeostasismodulator1
(CALHMI)ionchannel&↑ATPreleasefromtastebud• TarunoA,VingtdeauV,OhmotoMetal.Nature2013;495;223-6
• Tastes?mula?onyieldsdifferentreceptorcellsignaling• Tastant-↑ATP&effectviaK+&Ca+channels• Sweet/umami:↑GLP-1,NP-Y↓glucagon• Sour/salty:↑NP-Y,no∆GLP-1,glucagon• Biner:no∆NP-Y,GLP-1,glucagon• *NPY:neuropep?de-Y,GLP-1:glucagon-likepep?de
• GeraedisMC,MungerSD.JNeurosci2013;33:7559-64
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Tastesignaling&Neuropep3deSecre3on• Sweet,biner,umami↑calciumhomeostasismodulator
1(CALHMI)ionchannel&↑ATPreleasefromtastebud• TarunoA,VingtdeauV,OhmotoMetal.Nature2013;495;223-6
• Tastes?mula?onyieldsdifferentreceptorcellsignaling• Tastant-↑ATP&effectviaK+&Ca+channels• Sweet/umami:↑GLP-1,NP-Y↓glucagon• Sour/salty:↑NP-Y,no∆GLP-1,glucagon• Biner:no∆NP-Y,GLP-1,glucagon• *NPY:neuropep?de-Y,GLP-1:glucagon-likepep?de
• GeraedisMC,MungerSD.JNeurosci2013;33:7559-64
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Gusta3on–organisa3onofreceptorsSpa?alsegrega?onofsensesnot
evidentinhumans,althoughsomenervesthatsynapsetoT1Rprojecttorostralaspectsofthesolitarytractnucleus(andT2Rtocaudal)
Possiblesegrega?oninmice,but
nothumansScon,Neuron200548:455-64
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AlteredtasteOralandURTdisease(infec?on,malignancy)BurningmouthsyndromeHyposaliva?onIatrogenicDrugs:Many!
Chemotherapy Cyclophosphamide,Dacarbazine,Daunorubicin Doxorubicin,5FU,MTX,Pla?num,Vincaalkaloids
SystemicdiseaseCNS(temporallobetumors,epilepsy)GERDetcRenal–chronicfailureHepa?cfailureDeficiencystates(zinc)Psychiatric(includinghypochondriasis)
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SymptomBurdeninHNC:oralenergy&proteinintake• 43HNCpts,cross-sec?onal,prospec?vestudy• Medianage60;97.7%Caucasian,81%M;HNCStageIII28%,StageIV63%;
AllRTHNC,mean6862gy;CT93%,• feedingtube86%;tobacco81%,alcohol46%• VHNSS2.024hrdietdietaryrecall,protein,energyintakeusing
Mypyramid.com• GanserH,Touger-DeckerR,ParronJ.JSCC2012;July24
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AlteredtasteandheadandneckmalignancyCommon–upto100%-butmayarisebeforetreatment–duetotumor.
Reviewsuggestedupto89%ofpa?entspriortoRThavesometastedisturbance
RuoReddaandAllisCancTreatRev200632:541-7
Subjec?veassessmentpriortoRTsuggestedpar?allossofbiner(35%),salt(18%)and/orsweet(6%)
Maesetal,RadiotherOncol200263:195-201
Tastechangebegins~3weeksandinsomestudiesimprovesby8weeksofTX
YamashitaH,NakagawaKetalIntJRadiatOncolBiolPhys2006;66:1422-9YamashitaH,NakagawaK.Etal.2008
Secondmostcommoncomplaintinpa?entsajer3and6monthspost-RTHNC
MurphyBA,EpsteinJB2011
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Radiotherapy-associatedtastechangeEffectsontastequalityvariable
LossofsweetfirstBinerandsalt>sweet4“conven?onal”quali?esequallyaffectedUmamiaffected
Mossmanetal,19795:521-8
Maesetal,RadiotherandOncol200263:195-2001Zhengetal,FukuokaIgakuZasski200293:64-76
Shietal,AurisNasusLarynx200431:401-6Yamashitaetal,HeadandNeck2006June508-16RuoReddaandAllisCancTreatRev200632:541-7
YamashitaH,NakagawaKetal.2008Possiblyreflec?ng:
MethodofassessmentRadiotherapydose&technique
Lossofumamimayhavethestrongestcorrela?onwithQoLShietal,AurisNasusLarynx200431:401-6
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Alteredtaste:headandneckmalignancyRadiotherapytastechangeshighlyvariable:
“Soapy” “Burning” “Oily” “Powdery” “Chemical” “Awful”
Impactoftastechange: Reduceddietaryintake Weightloss ReducedQoL Poor(er)outcomes
Sandowetal,2006JDentRes200685:608-611
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Radiotherapy-associatedtastechangeTemporaleffectsvariable
Maximumlossoftasteat2/12,returnedby24/12
Maesetal,RadiotherOncol200263:195-201Tastedisturbances?llreportedat7yearspost-RT
Mossmanetal,IntJRadiatOncolBiolPhys19828:991-7)Normaltasteby6/12
Zhengetal,FukuokaIgakuZasski200293:64-764tastecuesreducedby3/52,returnedtonormalby4-8/12
Yamashitaetal,HeadandNeck2006June508-5164tastecuesreducedwithin1/12,normalby6/12
Sandowetal,2006JDentRes200685:608-611Possiblyreflec?ng:
MethodofassessmentRadiotherapydosageRadiotherapytechniquePa?entnumbers
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TasteChangeinBreastCancer• 25pts,TXdocetaxelorpaclitaxelorwithin6monthsofCT• mostcommonPRO:tastechange(8/10docetaxel;3/15paclitaxel)• Dysguesia:55%;badtaste27%,hypoguesia45,hyperguesia9%• Tastechangeaffectoralintake,irregularea?ngschedule,↓interestmeal
prepara?on• Behaviors:newrecipes,stronglyflavoredfoods,foodcravings,candybefore
meals,addinglemon,sweeteneddrinks,plas?cutensils,drinkwithstraw,brushteeth&tongue,bakingsoda/saltrinsing,an?bacterialmouthwash
• Selfmanagement:↑caloricintake,poorea?ngbehaviors,↑weight&associa?onofobesitywithpooroutcomes
• SpeckRM,DeMicheleA,FarrarJTetal.SupportCareCancer2013;21:549-55
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Nutri3onalissues&bodyweightinallo-BMTlong-termsurvivors• 441BMTsurvivorsofBMT,NSWAustralia
Symptom <2yrsBMTn=58
2-5yrsBMTn=159 >5yrsBMTn=224
Nausea 8(13.8%) 21(13.2%) 21(9.4%)
Vomi?ng 3(5.2%) 10(6.3%) 6(2.7%)
Cons?pa?on 10(17.2%) 15(9.4%) 41(18.3%)
Diarrhea 11(19.0%) 29(18.2%) 43(19.%)
Tastechange 26(44.8%) 53(33.3%) 55(24.5%)
Smellchange 19(32.8%) 34(21.4%) 35(15.6%)
Poorappe?te 16(27.6%) 29(18.2) 40(17.9%)
Mouthulcers 21(36.2%) 46(28.9%) 77(34.4%)
Drymouth 26(44.8%) 65(40.9%) 93(41.1%)
Median#symptoms 2(0-9) 1(0-9) 1(0-7)Smith J, Poon C, Gilroy N et al. Support Care Cancer 2017;25:137-44
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PrevalenceofCT-relatedproblems&HRQOL• 363(43%responserate);mixeddiagnoses,CTfor“cure”• Mostprevalentc/o:fa?gue(90%);changeinsmell/taste(69%)
• RelatedtoHRQOLsocial/emo?onaldomains• WaglandR,RichardsonA,EwingsSetal.SupportCareCancer2016:24:4901-11
Rank Problem %affected Severe Moderate Mild
1 Fa?gue 90% 11% 37% 42%
2 Changeintaste/smell 69% 11% 24% 34%
4 Troublewithsleep 55% 9% 21% 29%
5 Lowmood 56% 4% 16% 30%
9 Lossappe?te/interestinfood 54% 5% 17% 32%
10 Concentra?on,forget,confused 52% 3% 11% 38%
12 Soremouth/tongue 46% 6% 12% 20%
13 Diarrhea 39% 4% 12% 28%
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Oralcomplaints&dentalcareinSCT• Survey:101SCTadultpts(37%allo)(95%responseofsurvivors[possible
bias]);• 88pa?entsden?sts(59%response)• TimesinceSCTmean19mos(range:8-31)• AlloSCT:Meanmaxmucosi?sscore6.6(sd=3.3)
Bos-denBraberJ,Po�ngCMJ,BronkhorstEMeta.JSCC2015;23;13-9
Complaints Acute Chronic
Drymouth 70% 56%
Tastechange 86% 33%
Mucosi?s 96% 11%
Trimsus 14% 7%
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TasteandSmellinSCT
• 23pts(16atall?mepoints):baseline,Day30,Day80• Taste:0.32MNaCl;0.0056&0.018Mcitricacid;0.3Msucrose;
Olfactory:NIHtoolboxOdorIden?fica?ontest;QOL• ↓sensi?vityforNaCl,citricacidonD30• ↑sensi?vitysucroseD30• TastelargelyrecoveredbyD80• OlfactoryscoresunchangedbaselinetoD30• QOLimprovedbyD80,althoughsomeoralsymptomsremain
• AbasaeedR,ColdwellSE,LloidME,etal.JSCC2018;Apr27
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Oral health & QOL in cancer patients in hospice • 104terminally-illCApts(2.5-3wklifeexpectancy);medianage
66.0;M40.8%,F59.2%• OralProblemsScale(OPS):xerostomia,oralpain,tastechange&
func?onal/socialimpactonQOL;oralexam• Hyposaliva?on(98.1%),erythema(50%),ulcera?on(20.2%),fungal
infec?on(35.6%),otheroralproblems(44.2%).• Xerostomia,tastechange&oralpainimpactQOL(p<0.001,<0.042
&p<0.001,respec?vely)• Oralpainsignificantsocialimpact(p<0.001);ulcers↑pain• Erythemaassociatedwithfungalinfec?on&ulcera?on(p<0.0001)
• FischerDJ,EpsteinJB,YaoY,WilkieDJ.SuppCareCancer2013
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Flavor• combina?onofsensoryfunc?ons:
• Taste,texture,temperature,smell,visual,memory• Basicquali?es:Sweet,biner,salty,sour,umami• Otherquali?es:fat,spicy,water• Umami~good/desirableflavormayhavestrongestcorrela?onwithQOL• Impact:
– Interestinfood– alteredfoodintakeleadingtodietarydeficienciesorweightloss/
weightgain– Impairedqualityoflife
Chandrashekar J, Hoon MA, Ryba NJ. Nature. 2006 Yamashita H, Nakagawa K et al. Oral Oncol. 2008 Shi HB, Masuda M, et al. Auris Nasus Larynx 2004 Murphy BA, Epstein JB. Head Neck 2011
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FaTyAcidTaste• Fanytastethoughttomediateimportantenergy
intake• Medium&longchainFAreceptorGPR40(Ffar1)&
GPR120;ontastebudtypeI,IIcells• Animalstudy:FAtes?nglinoleicacid&oleicacid• IHC,nerverecording,behavioraloutcomeaffected• FAalsoshowntomodifybinertaste,butnot
mediatedbyGPR40/120• CartoniCYasumatsuK,OhkuriTetal.JNeurosci2010;30:8376-82
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DietaryAdapta3ons/Maladapta3ons• ↓quan?tyoffood• ↓highfiberfoods• ↓vitamin,mineral,protein&energy• ↑fatcontent• ↑caffeine&sugar• ↑cariesriskImpact:
– ↓interestinfood– alteredfoodintake– dietarydeficiencies,weightloss
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ImportanceofOralHealthOutcomes:• Oralhealthcondi?onsresultin:
• Alteredfunc?on• ↑Symptomburden• ↓qualityoflife• ↑costs
• Oralhealthinfluencesgeneralhealth:• Pain,taste,dysphagia;nutri?onaldeficits• Aspira?onmaycausepulmonarydisease• Periodon??sassociatedwithCAD• Psychosocialimpact:pain,esthe?cs,socialfunc?on
• ChangingExpecta?ons:• ↑HNCinyoungeradults• Reten?on&esthe?csofden??onisimportant
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TasteinChemotherapy• Consecu?vebreastCAptsadjuvantCT
– baseline,6thcycle,6&12months• TastedisturbancescommonduringCTv.baseline&v.tonoCT• DuringCT:dysgeusia(metallicordrugtaste,33%)+hypogeusia
(22%)• 6monthsF/U:tastechange(20%)• 12monthsF/U:mostreportedtastechange:hypogeusia(16%)• PI/GI↑ duringCT;mucosi?s:~20%,ulcer16%• Tastethemostdistressingoralsymptomin22%duringCT,andin
10%at12months• JensenSBetal.OralSurg2008
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TasteChangeinBreastCancer• 25ptsondocetaxelorpaclitaxelorwithin6mosofCT• mostcommonPRO:tastechange(8/10docetaxel;3/15paclitaxel)• Dysguesia:55%;badtaste27%,hypoguesia45,hyperguesia9%• Tastechangeaffectoralintake,ea?ngschedule,↓interestmeal
prepara?on• Behaviors:newrecipes,strongflavoredfoods,foodcravings,candybefore
meals,addinglemon,sweeteneddrinks,plas?cutensils,drinkwithstraw,brushteeth&tonguefrequently,bakingsoda/saltormouthrinsing
• Pa?entadapta?ons:some+/-:↑calorieintake,poorea?ngbehaviors,↑weight
• SpeckRM,DeMicheleA,FarrarJTetal.SupportCareCancer2013;21:549-55
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Taste&SmellChangeinCT• OutPt518CTsubjects,varioussolidCA,ques?onnaire• TSC:75%,>♀ 79%v♂59%,youngerpts• TSC>breastCA;CT:cyclophosphamide,5FU,epirubicin;
venorelbine• Tastechange:salty41%,sweet36%,biner24%,sour21%,
other48%• Smellchange:49%,greatestperfume,cookingsmells• ImpactofTSCassociatedwith(OR):
nausea4.0,vomi?ng1.7,oralproblems4.0,appe?teloss3.2,depression1.8
BernhardsonB-M,TischelmanC,RutqvistLE.SupportCareCancer200816:275-83
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Taste&Olfac3oninBCpa3ents• 69BCpa?ents,meanage52.4yrs,24post-
menopausal,post–sx62,pre-CT• Symptoms,smell(“Snffin’S?ks”)&tastetes?ng
(tastestrips)• Resultscomparabletonorma?vedata:• Nodifferenceinodorthreshold,odordetec?on,↓sensi?vityforsour,nochangeforsalt,sweet,biner;↑Tsizeassociatedwith↓smell,butnottaste;correla?onwithbinertaste&Her2+
• SteinbachS,HundtW,ZahnertTetal.SupportCareCancer2010;18:707-13
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Tastechangeincancerpa3ents
Under-reportedInfluenceofxerostomia:Correla?onspossible
MossmanetalIntJRadiatOncolBiolPhys19828:991-7Inokuchietal,Prac?caOto-Rhino-Laryngologica200295:1091-6
Zhengetal,FukuokaIgakuZasski200293:64-76Tonguevolume:Correla?onssuggested
Fernandoetal,ClinOncol(RCollRadiol)19957:173-8Yamashitaetal,HeadandNeck2006June508-516
Variability:unusualreportoflongtermcompletelossdespite½
tonguebeingsparedSaitoetal,Radia?onMedicine200220:257-60
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� Avoid use of metallic utensils � ↓ food with metallic or bitter taste (eg: red meat,
coffee, tea) � ↑ high-protein, mildly flavored foods (chicken, fish,
dairy products, eggs) � ↑seasoning & spices to enhance flavors � Serve foods at cold temperature � Practice good oral hygiene � If dry mouth provide saliva stimulation
1)StrategiestoImproveTasteandOdorAbnormali3es
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� Aim: to spare radiation of salivary glands, and reduce high dose RT to oral tissues when possible
2)IMRT
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TherapyDietarycounselling/modifica?on
Seasoning,avoidunpleasantfoods,extenddietarychoice(pleasingcolor,form,smell,texture) PeregrinJAmDietAssoc2006106:1536-40
Foodprepara?on:spice/flavoring,increaseumamiflavorManagexerostomiaManageoraldiseaseZincsulphate
Reducedseverity&dura?onoftastedysfunc?on(18pa?ents)Ripamon?etal,Cancer199882:1938-45
Butbenefit(NS)observedinlargerstudy(169pa?ents;lowerdose)Halyardetal,IntRadia?onOncologyBiolPhys200767:1318-22
Medica?ons:clonazepam,gabapen?n,megestrol,THC(Marinol),CBDThorneT,OlsonK,WismerW.JSCC2015;23:284
ManageOral/OPCpainandnauseaifpresent
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SupplementsandTaste
• Zincmaypromotetastebudprolifera?on• Zinc(50mg/TID)mayaffecttasteindependentofserumzinclevels
• HeckmannSM,HujoelP,HabigerS.JDentRes2005;84:35-8• TakaokaT,SakukuraN,UedaC.AurisNasusLarynx2010;37:190-4
• Alphalipoicacidmayaffectneuropathy• Alphalipoicacid(200mg?d)fortastedisorders:91%improved,46%
resolved• FemianoF,ScullyC,GomboF.IntJOMFSurg2002;31:625-8
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� Variable results in trials and non homogeneity
Study
Design Regimen Outcomes
Mossman,1978
Caseseriesn=7,postHNRT
25or100mg/dayzincfor2-6months
Improvementinobjec?vetaste
Silverman&Thompson,1984
Caseseriesn=30;postHNRT
100-150mg/dayzincforatleast1month
Improvementinsubjec?vetaste
Silvermanetal,1983
RCTn=19;preHNRT
18mgqdzincfordura?onofRT
Nodifferenceinobjec?vetasteEarlierrecoveryofsubjec?vetaste
Ripamon?etal,1998
RCTn=18;inHNRT
45mg/dzincun?l1monthpostRT
Lessobjec?vetastedisturbsduringRT.Earlierrecoveryofobjec?vetaste
Halyardetal,2007
RCTn=169;preHNRT
30mg/dzincDuringRTand1monthajer
Nodifferenceinsubjec?vetastedisturbanceNodifferenceinrecoveryoftaste
Lyckholmetal,2012
RCTn=58;duringchemo
220mgbidzincDuringchemo
Nodifferenceintastealtera?onsLonger?metorecoveryofsmellaltera?ons
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� Naturalsubstances:Synsepalumdulcificum(miraclefruit)àbindstotastereceptorstogenerateasweetsensa?on,thusmaskingsomeunpleasanttastesforashortdura?on
� Chlorhexidinemayblockbinertastereceptor� Marinol(THCcannabinoid)àenhancesfoodenjoymentviaendocannabinoidreceptorsthats?mulatetheorosensoryrewardpathway
� Megace:20-40mgBID
4)OTHER:WHAT’SNEW?
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ZincSulfateTrialinHNRT• 169ptsrandomizedtoZincSO445mg/dduringRT+1
monthajervplacebo• TasteoutcomesassessedwithWickhamques?onnaire
(WickhamRSOncolNursForum1999;26:697-706)
• 73%onZincv84%reportedtastealtera?ons(p=0.16)• Complextastechange:absence16%;biner8%;salt4%;
sweet5%;metallictaste10%;wrinencommentssoapy,oilyorburningtaste
• HalyardMY,JatoiA,SloanJA,etal.IntJRadiatOncolBiolPhys2007;67:1318-22
• Benefitsontastereported;tastetes?ng:tastethresholds• Ripamon?C,ZeccaE,BrunelliCetal.Cancer1998;82:1938-45
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Clonazepam
• Gabanergicdrugsmodifytasteinanimalstudy• Staros?kMR,RebelloMR,ConerKA.PLoSOne2010;5:e13639
• Clonazpam:gabaAagonistaffecttastechangeassociatedwithBMS• GrushkaM,EpseinJ,MonA.OralSurgOralMedOralPathol1998;86:557-61
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THC&ChemosensoryDisorders• 46pts,advancedcancer;21completedstudy,11dronabinol
(Marinol)[THC],10placebo,RX18days• 2.5/5.0/10mgbid• THCindicated:nausea,appe?te• THCvplacebo:
– ↑apprecia?onoffood73%v30%– ↑taste55%v10%– ↑appe?tep<0.05,↑sleepquality,– nooverall∆QOL
• BrisboisT.AnnOncol2011• DeLucaMNeuropharmacol2012
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Megestrol
• RT+/-CTadvancedcaner;100pts,randomizedtrialmegestrol,PROs
• 46megestrolduringRT,4ajerRT;50placebox3mos• nodifferenceacutetoxicityofRT;acutetoxicityassociated
withwghtlossplacebobutnotmegestrol• megestrol↑appe?te,↑taste,↑wght(p=0.000);↑smell
(p=0.02);• noSE
• ErkurtE,ErkisiM,TunaliC.JExpClinCancerRes2000;19:431
• Megace480mg/d• ThorneT,OlsonK,WismerW.JSCC2015;23:284
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Localmeasuresforblockingabnormaltaste
• Foodprepara?on:– herbs,spices,sweetener,acidtofood
• Maskingagents:– mouthwashes,candy,gum
• Chela?ng/blockingagents:– chlorhexidinemayblocksalt&binertaste
• MiracleFruit(Synsepalumdulcificum):– Glycoprotein“miraculin”,maymodifybinerandsourtosweettaste;blockbiner?
– ThorneT,OlsonK,WismerW.SupportCareCancer2015;23:2843-51– JomaI,RenkenRJ,TerHorstGJ.CancerTreatRev2015;41:179-86
– SwamyKB,HadiSA,SekaranM.JMedFood2014;17:1165-9
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Localmeasuresforblockingabnormaltaste• Blockingbinertaste:TAS2R2receptorinhibitors;belowaffectsome
binerreceptors,butnotall– 4-(2,2,3-trimethyl-cyclopentyl)butanoicacid(GIV3727)– gama-aminobutryicacid– 6-methoxyflavones– probenecid– MSG– Na,Na-bis(carboxymethyl)-1-lysine(BCML)– phospa?dicacid-tactoglbulin– adnenosine5’-monophosphate
• Blockingsweettaste:– Lac?sole– Gymnemicacid
• Blockingsweetandbiner:Chlorhexidine• Changingacidtosweet/blockingbiner:Miraclefruit?
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MiracleFruit• MiracleFruit(Synsepalumdulcificum):
– Glycoprotein“miraculin”maymodifybinerandsourtosweettaste
– BindstoT1R2-T1RXasantagonistatneutralpH&agonistatacidpH
– JomaI,RenkenRJ,TerHorstGJ.CancerTreatRev2015;41:179-86– SwamyKB,HadiSA,SekaranM.JMedFood2014;17:1165-9
– KoizumiA,TsuchiyaA,NakajimaKetal.ProcNatlAcadSci2011;108:16819-24
– Transduceacidictosweetsignal;maskunpleasanttaste,increasepalatabilityofsomefoods
– TasteimprovementMiraculinvplacebox2wksin8CTptsonCTcrossoverstudywithimprovementonac?vearm
– WilkenMK,Sa?roffBA.ClinJOncolNurs2012;16:E173-7
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Preven3onandTreatmentofNeuropathy• Noprovenprophylaxis• Management:basedonpainmanagementofneuropathic
pain• Centrallyac?ngmedica?ons:
– clonazepam,gabapen?n,pregabalin,duloxetene,tricyclics• Topicalagents:
– receptorblocking/s?mula?ngagents– centrallyac?ngmedica?ons,trial:baclofen,amitriptyline,ketamine
• Nerves?mula?on
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Evidence-BasedStrategiesforOralComplica3onofCancerTreatment
knowledgeoftheburdenofillness,preven?onandtreatmentoforalcomplica?onsassociatedwithcancertherapiesisnecessarysystema?creviewsofthemostcommonoralcomplica?onswerecompletedbytheOralCareStudyGroupofMASCC/ISOO.Managementrecommenda?onandguidelineclassifica?onwasbasedoncriteriaoftheASCOra?ngthelevelofevidenceandgradeofrecommenda?on
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Resources:• MASCC.com• NCI-PDQ:oralcare,mucosi?s• EpsteinJB,BaraschA.Tastedisordersincancerpa?ents:
Pathogenesis,andapproachtoassessmentandmanagement.OralOncol2010;46(2):77-81.
• EpsteinJB,MurphyBE.Oralhealthandsurvivorship:Lateeffectsofcancerandcancertherapy.In:TheMASCCTextbookofCancerSuppor?veCareandSurvivorship.OlverIN(Ed).Springer,NewYork,ISBN978-1-4419-1224-42010;pp399-406.
• DaviesAN,EpsteinJB(Eds).OralComplica?onsofCanceranditsManagement.OxfordUniversityPressInc,GreatClarendonStreet,OxfordOX26DP;OxfordUniversityPressInc,NewYork,2010;ISBN978-0-19-954358-8.
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Dysgeusia(5)Dysgeusia:anabnormalorimpairedsenseoftaste,anunpleasantaltera?onintaste,oradistor?onor
perversionoftasteMeanweightedprevalenceofdysgeusia:
Chemotherapyonly=56.3%Radiotherapyonly=66.5%CombinedRTandCT=76%
Management:Zincgluconate(LevelofevidenceII,recommenda?ongradeC)Sugges?ontoNOTusezincgluconatetopreventdysgeusiainHNCpa?ents,althoughthisisbeneficialinanon-
canceridiopathicdysgeusiacohortAmifos?ne(LevelofevidenceII,recommenda?ongradeB)RecommendNOTtouseamifos?nesolelyforthepreven?onofdysgeusiaHNCpa?entsDietarycounseling(LevelofevidenceII,recommenda?ongradeB)
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OralFungalInfec3on(6)Oralcandidiasis:themajorityoforalfungalinfec?ons
presenta?on:pseudomembranouscandidiasis,erythematouscandidiasis,hyperplas?ccandidiasis,angularcheili?sWeightedprevalenceofclinicaloralfungalinfec?on(alloralcandidiasis)
pre-treatment=7.5%duringcancertreatment=39.1%ajertheendofcancertherapy=32.6%
Weightedprevalenceoforalcandidiasisbycancertreatmentduringheadandneckradia?ontherapy=37.4%duringchemotherapy=38%
Weightedprevalenceoforalcoloniza?onwithfungalorganisms
Beforecancertreatment=48.2%duringcancertreatment=72.2%ajercancertreatment=70.1%.
Weightedprevalenceoforalfungalcoloniza?onbycancertreatment
duringchemotherapy=72.8%duringradia?ontherapy=74.5%
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OralfungalInfec3on(5)ManagementWeightedprevalenceofclinicaloralfungalinfec?onduringcancertherapybypreven?ve
treatmentregimenFluconazole=1.9%Amphotericin=2.3%Itraconazole=1.5%Nysta?nalone=6%Clotrimazoleandnysta?n=14.6%Amifos?ne=28.9%Placebo/Notreatment=20.3%
Topicalan?fungalagents(levelofevidenceII,recommenda?ongradeC)inconsistentefficacyoftopicalan?fungalagentsasprophylaxis.Norecommenda?onpossible.Systemican?fungalagents(levelofevidenceI,recommenda?ongradeA)Recommendfluconazoleforthepreven?onoforalcandidiasisincancertherapy.
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OralViralInfec3on(7)PrevalenceofHSVoralandperioralinfec?on:Weightedprevalenceinpa?entstreatedwithchemotherapyforhematologicmalignanciesPa?entswithoralulcera?ons–samplingoralulcera?ons=49.8%Weightedprevalenceinpa?entstreatedwithradiotherapyPa?entswithradiotherapyonly-samplingoralulcera?ons*=0%Pa?entswithradiotherapy+CT-samplingoralulcera?ons=43.2%ManagementAcyclovir&valacyclovirrecommendedforthepreven?onofHSV(Gradeofrecommenda?onA,levelofevidenceI)Preven?on:acyclovir(800mg/day)orvalacyclovir(500-1000mg/day)valacyclovirmaybesuperiortoacyclovirintoxicity&cost(dependsontherouteofadministra?onofacyclovir—POor
IV)*-Simpleprevalenceispresentedasthisfindingisbasedonasinglereportintheliterature.
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DentalDisases(8)• Weightedprevalencefordentalcariesinpa?entstreatedwithcancertherapy• Allstudies=28.1%• Chemotherapyonly=37.3%• Post-radiotherapy=24%• Postchemotherapyandradiotherapy=21.4%• • Weightedprevalenceseveregingivi?sinpa?entsundergoingchemotherapy=20.3%• • Weightedprevalencedentalinfec?on/abscessinpa?entsundergoingchemotherapy=5.8%• • Management• Recommendfluoridetopreventdentalcariesinpa?entswhoarepost-radiotherapy.Effec?veregardlessofthetypeofdeliverymethod.(LevelofEvidenceII,Gradeof
Recommenda?onB).• • Recommendchlorhexidinetoimproveoralhygiene,poten?alsideeffects:toothstaining,increasedcalculus,tastechanges(LevelofEvidence:II,Gradeof
Recommenda?on:B,)• • Suggesttheuseofresin-modifiedglassionomer,compositeresinoramalgamrestora?oninpa?entswhohavebeentreatedwithradiotherapy(LevelofEvidenceIII,Grade
ofRecommenda?onB).• • Noguidelinepossibleduetothelackofwelldesignedstudiesregardingthebenefitsoftoothpaste,pre-cancertherapydentalinterven?on,honey,andcheeseondental
health(LevelofEvidenceIII,Gradeofrecommenda?onC).•
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Osteoradionecrosis(ORN)(9)• Weightedprevalenceinconven?onalRT=7.4%• WeightedprevalenceinintensitymodulatedRT=5.2%• WeightedprevalenceinRTandchemotherapy=6.8%• Weightedprevalenceinbrachytherapy=5.3%• • Themajorityofcasesinvolvethemandible.• • Management• • Prac??onersshouldu?lizetheirclinicalexperienceandexper?seisdeterminingop?malmanagementfortheirpa?ents
rela?vetoORNofthemandibleorthemaxilla.• • Noguidelineispossibleregardingtheuseofprophylac?cHBOtherapyforthepreven?onofORNinpa?entsrequiringpost-
RTdentalextrac?ons• (LevelofevidenceIII,recommenda?ongradeC)• • TheuseofsingletherapyHBOtherapyforthetreatmentofORNisNOTrecommended(LevelofevidenceII,
recommenda?ongradeB)• • Noguidelinespossibleforotherpreven?onandtreatmentstrategiesforORN•
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TreatmentforOralMalodor1• Managementoflocaldentalpathosis
• restora?ons,cariesorpulppathology;periodontaldisease;denturehygiene
• Managementoforalsoj?ssuecondi?ons• Diagnosis/ManagementofENTpathosis
• sinusi?s,tonsoliths,postnasaldrip)
• Dietarysugges?ons:• Avoidodiferousfoods• Avoidtobaccoandalcohol• Reducetheconsump?onofredmeatanddairyproducts• Avoidstayinghungry-healthysnacksbetweenmeals
• Goodoralhygiene• Homecareincludingbrushing,flossing,denturecare,tonguescraping• Regularprofessionalcleaning
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TreatmentforOralMalodor2• Maintainmouthmoisture
– hydra?on– S?mula?on:sugarfreegum/candy– Sialogogues
• An?microbialmouthwashes– Chlorinedioxide,cetylpyridinuimchloride,phenolicoil,zinc
chloride,triclosan,chlorohexidineetc• Medicalevalua?onofsystemiccondi?ons
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ManagementofOlfactoryDisorders Pharmacotherapy
• Systemic&topicallyappliedcor?costeroidsformucosaledema/nasalpolyps
• An?bio?cs,decongestants&an?histaminesforchemosensorylossduetosinusinfec?on&allergicrhini?s
• Benzodiazepines,tricyclican?depressants,an?convulsantsmaybehelpful:– clonazepam0.5-2mghs– amitriptyline25-100mghs– gabapen?n300-1,800mgperday
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ManagementofOlfactoryDisordersSurgery• Endoscopicnasal/sinussurgeryMiscellaneous• counselingonsmoke&naturalgasdetec?on• labelingoffoodtotrackspoilage• Baseline&repeatchemosensorytes?ng*olfactoryfunc?onmaytakeyearsormaynever
recover,followingpost-viralinfec?onorheadtrauma
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Conclusions:TasteandSmell
ImpactuponQoLKnownphysiologydoesnotmatchobserva?onsofpostRTtastedysfunc?on–
whyselec?veinquality?VolumeofRTmaycorrelatewithtastedysfunc?onSalivaryfunc?onseemsapartofthepresenta?on:(tastedysfunc?onresolves,
xerostomiadoesnotorxerostomiaresolvesandtastedoesnot)ZincsulphatehasuncertaineffectsMethodsthatlessen?ssuedamagemaybethewayforward(preven?on)
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Summary:ReporttotheNa3ononStatusofCancer2013• ↓Deathrates2000-2009:1.8%/yrM,1.4%/yrF;<14yrsage1.8%/
yr• ↓ overalldeathsduetocancerforallbutmelanoma,liver,
pancreas&uterus• 2000-9↓incidenceoverallcancers0.7%/yrmen;stableinwomen,
↑0.6%children• 2000-9↑incidenceofHPVOPCwhitemen/women;vulvawhite&
blackwomen• US:48.7%girls13-17HPVvaccinated,32%3doses;Canada
50-85%,UK/Australia70%• Obesityrelatedto33%ofcancers
• JemalA,SimardEP,DorellCetalJNCI2014;105
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DietaryModifica3onsforCancerPa3ents
Diet TextureModifica3on
Regulardiet Allfoodsallowed
Dysphagiadiet,Advanced Soj-solidfoodsthatrequirechewing
Dysphagiadiet,mechanicallyaltered Cohesive,moist,semisolidfood,limitedchewingrequired
Dysphagiadiet,pureed Homogenous,cohesive,pudding-like
Liquiddiet Liquidsupplements
Epstein JB, Huhmann M. J Am Dent Assoc 2012;143:588-92
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Na3onalDysphagiaDietDietConsistency Descrip3on
NDD-1(DysphagiaPureed) Soj,pudding-likeconsistency,smooth,nolumps
NDD-2(Dysphagiamechanicallyaltered)
Moist,soj,textured(eg:finelydicedmeats,soj-cookedvegetables,cannedfruit,moistcereals
NDD-3(Dysphagiaadvanced) Mostregularfoods,exceptveryhard,s?ckyorcrunchy
Liquidconsistencies
Spoonthick
thickenedtopuddingconsistency;remainonaspooninasojmass
Honey-like thickenedtoconsistencyofhoney,flowoffaspooninaribbon
Nectar-like consistencythatcoatsanddripsoffspoon
Thinliquids Allliquids
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LiquidNutri3onalSupplementsType Descrip3on Examples
Readytodrinkliquidnutri?onal
Premixedliquid Ensure,Boost,Enlive,ResourceBreeze,IsopurePlus
Milk-based Poweraddedtomilk Carna?onInstantBreakfast(with/outsugar),Scndishake,proteinpowder
Disease-specificliquid Premixedliquid,diseasespecificingredients
Diabe?c:Glucerna,BoostGlucoseControlRenal:Nepro,Suplena,Renalcal
Modular Powderorliquidaddtofood(proteinorcaloricsupplement
Liquid:Benecalorie,Promod,Pro-statPowder:Beneprotein,UnjuryProtein
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DietaryInterven3ons:Latecomplica3onsofHNCTherapyComplica3on DietaryInterven3on
LossofAppe?te Small,frequentmeals;limittonon-carbonatedbeveragesbetweenmeals,liquidsupplements
Tastechange Tartfood(citrusiftolerated),flavorfulseasoning,marinatemeats,chicken,fishinfruitjuice,soysauce,sweetwine,Italiandressing,addumamiflavors
Mucosi?s Avoidspicy,acidic,rough,saltyfoods
Hyposaliva?on Soj,moistfoodseasytoswallow(sakes,bananas,applesauce,noodles,icecream,yoghurt,eggs,gravy,broths,Chop,puree,blenderfoods;drinkliquidswithmealsAvoiddryfoods,simplesugars
Trismus/dysphagia Sojfoods,smallbites,blender,supplements
CariesRisk Avoidsugarsweeteneddrinks,gum,candy;fruitandjuicewithmeals,paircariogenicfoodswithcariosta?c(peanutbuner,cheese,milk,cereal,sweetsonlywithmeals,xylitolsweetnerBrushteethbeforemeals
Epstein JB, Huhmann M. J Am Dent Assoc 2012;143:588-92
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EnteralFeedingRoute Indica3ons
GastricNasogastrictubePercutaneous(endoscopic)GastrostomyTube(PEG)Gastrostomytube
Shortterm,localirrita?onEndoscopicallyplacetube,leastinvasivepermanentfeedingtubeSurgicallyplacetube,placedduringSXorifendoscopicplacementnotpossible
SmallbowelPercutaneousendoscopicjejunostomytubeJejunostomytube
Endoscopicallyplacetube,usedifesophagusorgastricSXplannedSurgicallyplacedtube,placedduringSXorifendoscopicplacementnotpossible
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Approachtomanagement:
• Ifitworks,keepdoingit…• Ifitdoesn’twork,stopdoingit….• Ifyoudon’tknowwhattodo,don’tdoanything…
• (Andofcoursedon’trefertoasurgeon![unlesssurgeryisneeded])
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Cachexia/anorexiainCancerpa3ents• upto90%ofadvancedcancer• Lossofadipose?ssue/musclemass• Cancerbiology,tumorgrowth• Therapy:nausea,vomi?ng,flavor,appe?te• Changeintaste,lackofhunger,lackoffoodenjoyment• ↑inflammatorycytokinesassociatedwith:↓wght,fa?gue/
energy;physical/cogni?vedecline• Mouthcondi?on(dentalstatus),mucosi?s,salivafunc?on• Taste/smell/touch/temperature
• ReuterSC,Mar?nJH.ClinPharmacokinet2016;55:807-12
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Metabolismof2-AGandAnandamide
LiC,JonesPM.PharmacolToxicol2011;129:307-20
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PathwaysofCannabinoidReceptorac3va3on
LiC,JonesPM.PharmacolToxicol2011;129:307-20
Blueline-inhibi?on;Redline-↑ac?va?on
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LegendtoTableonSignalingPathwaysofCB1/2
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CannabinoidsandTaste
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CannabisinCancerCachexia-Anorexia• Systema?creview:26papers• Tetrahydrocannabinol(THC),cannabidiol(CBD)• Routesofdelivery:inhala?on,oral,mucosalabsorp?on• THClevels~thosebyinhala?onbyoral&GI;firstpassmetabolism<10%• THClipophyllicfatuptake;half-life~22hr• Distribu?oninfatvariable,affectedbycachexia?• Hepa?cmetabolism:cytochromep450;urinaryclearance(range2hrs-20wks)• GIabsorp?onaffectedbyGIfunc?on,mucosalabsorp?on• ↑appe?te/wghtgain
• NelsonK,WalshDJPalliatCare1994;10:39-97;• PlasseTF,GorterRW.PahrmacolBiochemBehav1991;40:695-700.
• Evidenceequivocalforuseincachexia-anorexiasyndrome• ReuterSC,Mar?nJH.ClinPharmacokinet2016;55:807-12
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Ac3onofCB1Receptor
LiC,JonesPM.PharmacolToxicol2011;129:307-20
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GhrelinandCannabinoids(1)• Ghrelin:circula?ngbrain&gutpep?de
– ↑growthhormonesecre?on&appe?te,– mediatedbygrowthhormonereceptors?mula?on&K(AMPac?vatedkinase)
• CBDs:orexin(hypocre?n)regulatesarousal&appe?te• Ghrelin,Lep?n&CBDs
– ↑AMPKhypothalamamus– ↓AMPKinliver&adipose?ssue– sugges?ngAMPKs?mulatesappe?te&↑peripheraleffectsofghrelin&CBDs
• IntactghrelinsignalingneededforeffectsofCBDsonAMPK• LimCT,KolaB,FeltrinDetal.MolecCellEndorcinol2013;365:303-8
• KolaB,WinmanG,BodnarIetal.FASEBJ2013;27:5112-21
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Lep3n/Grhelin:EnergyBalance
DNF:brainderivedneurogenicfactorCART:cocaine-amphetamineregulatedtranscriptCRH:cor?cotrophinreleasinghormoneGALP:galanin-likepep?deMCH:melaninconcentra?nghormoneNPY:neuropep?deYNT:neurotensinPOMC:pro-opiomelatoninOrexin:neuropep?de:alertness,appe?te
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CannabinoidsandTaste• Ratstudy:sweet/biner,THC&CB1antagonist(AM251)
– THC↑sucrosehedonicresponse– ↓rejec?onofquinine– ↑palatability&intakeofallfoods
• AM251reversedresponsetoTHCsuppor?ngac?onviaCB1receptor JarrenMMetal.PhysiolBehavior2007;90:425-30
• BlockingCB1↓mo?va?ontoobtainfood• Highlypalatablefoods?mulatesdopamine(DA)innucleus
accumbens(NAc)• effectonDAintasterxtosucrosevaversive–quinine&NaCl• THC↑sucroseeffect&↑DAinNAc• CB1↑hedonictaste(sweet)butnoeffectonaversivetaste
• DrosteSM,SalandSk,SchlinerEK.PharmacolBiochemBehav2010;95:443-8• DeLucaMA,SolinasM,BimpisidisZ,etal.Neuropharmacology2012;63:161-8
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B-caryophyllene(BCP):Dietaryphytocannabinoid• BCPac?vatePPAR-a&-yreceptors&inhibittoll-like
receptors• ↓immune/inflammatoryprocesses;synergywithµ-opioid
receptor,antagonistnico?nic-acetylcholinereceptors,noeffectserotonergic/GAGAergicreceptors
• Effects:cardio-,nephro-protec?ve,an?oxidant,an?-inflammatory,an?microbial,immune-modulator;nausea/vomi?ng;neuropathicpain
• Poten?aleffect:neurologicfunc?on,neurodegenera?vedisease;taste;nausea/vomi?ng
• Oralbioavailability,lipophyllic• SharmaC,AlKaabiJM,NurulainSM,etal.CurrPharmDes2016;22:3237-64
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PPARreceptors
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NeuraleffectsTetrahydrocannabivarin:Foodreward/aversion
• Tetrahydrocannabivarin:CB1antagonist• 20volunteers,fMRI,responsetovisual&tastes?muli(visual/
tastechocolate&aversiveresponsepictureofmoldystrawberriesorstrawberrytaste)
• Nodifferenceinsubjec?vera?ngsoftaste(CB1vplacebo)• fMRI↑responsetochocolate&↑responsetoaversive
s?muli• CB1antagonist↑neuralresponseto+&-s?muli;poten?al
forweightgainandweightloss• TudgeL,WilliamsC,CowenPJetal.IntJNeuropsycholpharmacol2014;18(6)
• TudgeL,WilliamsC,cowenPJ,McCabeC.IntJNeuropsychopharmacol2015;
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THC-inducedtasteavoidanceinratmodel
• THCaversivetastenotmediatedbyκ-opioidreceptor• Noeffectonaversivetasteseeninadults,minor
inconsistenteffectinadolescentrats• FlaxSM,WakefordAG,ChengKetal.Psychopharmacology2015;232:3193-201
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THC&Cannabidiolicacid(CBDA):Acutean3cipatorynausea• Ratmodel;nausea&tasteavoidancetest• THC↓condi?onedtasteavoidance,effect↓byCBDA• Nausea↓byTHC/CBDAindependently&together;centrally
mediatedatthevisceralinsularcortex• Suggestedvalueasan?-nausea
• RockEM,LimebeerCL,ParkerLA.Psychopharmacology2015;232:4445-54
• Noeffectonaversivetasteinadults,inconsistenteffectinadolescentrats
• THCaversivetastenotmediatedbyκ-opioidreceptor
• FlaxSM,WakefordAG,ChengKetal.Psychopharmacology2015;232:3193-201
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Cannabinoidsandhedonictasteresponse• BlockingCB1↓mo?va?ontoobtainfood• Highlypalatablefoods?mulatesdopamine(DA)in
nucleusaccumbens(NAc)• AssessedTHCeffectonDAontastereac?vitytosucrose
vaversive–quinine&NaClinrats• THC↑sucroseeffect&↑NAcDA• CB1↑hedonictaste(sweet)butnoeffectonaversive
taste• DrosteSM,SalandSk,SchlinerEK.PharmacolBiochemBehav2010;95:443-8
• DeLucaMA,SolinasM,BimpisidisZ,etal.Neuropharmacology2012;63:161-8
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CannabinoidsandTaste• 57adults,acutedosetrial(3days)• Salivaflowrate:–vecorrela?onwithplasmadruglevelin
singledosearm• Tastetes?ng:noeffect• But+selfreportof↑tasteresponse&↑hedonics
• ManesRD,ShawLM,EndelmanK.ChemSenses1994;19:125-40
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THCpalliateschemosensorychangeincancerpa3ents
• Pilotstudy:THC(2.5-10mgvplaceboBID)x18days(n=24/22);21completedstudy
• Taste/smellsurvey,3dayfoodrecord,appe?te,macronutrientpreference,QOLques?onnaire
• ↑chemosensorypercep?on(p=0.026)• foodtastedbener(p=0.04)• ↑appe?te(p=0.05)• ↑caloriesasprotein(p=0.008)• ↑qualityofsleep&relaxa?on(p<0.05)• ↑QOL&totalcalorieintakeTHC&placebo
• BrisboisTE,deKockIH,WatanageSMetal.AnnOncol2011;22:2086-93
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CannabinoidsEnhanceSweetTaste
• Cannabinoidsact@CB1receptorsinhypothlamus/limbicforebraininduceappe?te&s?mulatefoodintake
• Endocannabinoidsinplasmainversetolep?n• Tasteperipheraltargetoflep?n&cannabinoids• CB1&T1r3receptorsontastecells• Lep?n↓sweettasteinmice• Cannabinoids↑sweettaste,noeffectonsalt,sour,biner,umami
• YoshidaR,OhkuriT,JyotakiM,etal.ProcNatlAcadSciUSA2010;107:935-9
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Alteredtasteduetosmokingsubstance• 1250opportunis?callyrecruited(study1)• 76recruitedabstainers,cannabis(recrea?onalanddaily
users)• Tasteassessed:Sweet,salt,sour,biner,spicy• Mul?pledrugusers&cannabisusers↑preferenceforsalt/
sour• Dailycannabis&tobaccousers↑preferenceforsweet,spicy• Pastusersofcannabismayhavedifferentresponsesto
cannabinoidsthanpriornonusers
• DoveyTM,BoylandEJ,TraynerPetal.Appe?te2016;107:1-8
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CannabinoidsandTaste• Dronabinol(2.5mgBID)aloneorcombinedwithmegestrol
(800mg/d)vmegestrolalone• 469ptswithcancerrelatedcachexia• 49%reported↑appe?tewithdronabinol• Noeffectseendronabinolorcombina?onvmegestrol
• JatoiA,WindschitlHE,LoprinziCLetal.JCO2002;20:567-73
• DbleblindstudyTHC(2.5mg)with/withoutCBDBIDvplacebofoundnodifferences
• Noeffectduetodosing?;individual?tra?onmaybeneeded• StrasserF,LujnerD,PossingerKetal.JCO2006;24:3394-400
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THCandtaste• 46pts,advancedcancer;21completedstudy,11dronabinol
(Marinol)[THC],10placebo,RX18days• 2.5/5.0/10mgbid• THCindicated:nausea,appe?te• THCvplacebo:
– ↑apprecia?onoffood73%v30%– ↑taste55%v10%– ↑appe?tep<0.05,↑sleepquality,– nooverall∆QOL
• BrisboisT.AnnOncol2011• DeLucaMNeuropharmacol2012
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CannabisforAppe3teS3mula3on
• Survey204pallia?vecare/cancerpa?ents;13%medicinalcannabis(n=26)
• Ofpriorusers:givenforpain(n=9),appe?teloss(n=9);psychologicalproblems(n=5);insomnia(n=5),nausea(n=2)
• Tablets/capsulespreferred71%,mouthspray42%,vaporiser41%
• LuckenT,PhillipsJ,LintzerisN,etal.InternMedJ2016;46:1269-75
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Macro-osmia
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CannabinoidsandOlfac3on• THCapprovedinEUforAIDS-associatedanorexia• Addic?onpoten?al,incompleteunderstandingof
mechanismsofac?vity• Hunger↑sensorypercep?on~↑foodintake• THC/CBD↑odordetec?on,↑foodintakeinmice• CB1receptorsoncor?calglutamanergicneuronsproject
totheolfactorybulbinmice(roleinhumansunknown)• Soria-GomezE,BellocchioL.NatNeurosci2014;17:407-15
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OlfactoryBulb
Olfactorybulb:MCL-mitralcelllayer;GCL-granularcelllayerOSN-olfactorysensoryneuron;MC-mitralcellsPCG(inhibitory)periglomerularcells;GC-(inhibitory)granularcell Saria-GomezE.MolecCellEndocrinol2014
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Hormone/nutrientmodula3onofolfac3on
GLT-glucosetransporter;Kv1.3-voltagegatedKchannel;MOB-Mainolfactorybulb;AOC-anteriorolfactorycortex;PVN-paraventricularhypothalamus;LH-lateralhypothalamus;VMH-ventromedialhypothalamus;Arc-arcuatenucleusSaria-GomezE.MolecCellEndocrinol2014
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Endocannabinoids*andOlfac3on
S?mula?onofolfactorypercep?on&foodintake.Presysnap?cCB1receptors.CB1s?mula?on↓glutaminergicreceptors↓inhibi?onofolfac?on
Saria-GomezE.MolecCellEndocrinol2014
*
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ImpactofAnalgesicsonOlfactoryFunc3on• 100chronicpainpts;95healthycontrolswithno
analgesics• Olfactorytes?ng(CNI)“Sniffins?cks”test,odor
threshold&iden?fica?on;intensity(VAS);CNVintranasals?mula?on
• Chronicpainopioid&nonopioid(ajercontrolforneuropathy/chronicpainmedica?on)significantlyaffectCNI,Vsensoryfunc?on
• Mechanism:viaopioidreceptorsinCNVganglionorCNI/Vinterac?on
• MizeraL,GossrauG,HummelT.EurJPain2017;21:92-100
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TherapyDietarycounselling/modifica?on
Seasoning,avoidunpleasantfoods,extenddietarychoice(pleasingcolor,form,smell,texture) PeregrinJAmDietAssoc2006106:1536-40
Foodprepara?on:spice/flavoring,increaseumamiflavorManagexerostomiaManageoraldiseaseZincsulphate
Reducedseverity&dura?onoftastedysfunc?on(18pa?ents)Ripamon?etal,Cancer199882:1938-45
Butbenefit(NS)observedinlargerstudy(169pa?ents;lowerdose)Halyardetal,IntRadia?onOncologyBiolPhys200767:1318-22
Medica?ons:clonazepam,gabapen?n,megestrol,THC(Marinol),CBDThorneT,OlsonK,WismerW.JSCC2015;23:284
ManageOral/OPCpainandnauseaifpresent
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TasteFunc3oninOncology• Themouthisapartofthebody• Cri?calroleindiet/nutri?on/sustenanceandQOL
• Controlledtreatment&prophylac?cstudiesindicatedwithpharmaceu?calproduct
• Whilereceptorsandmechanismofac?onarebecomingbenerunderstood,manymoreques?onsthananswers
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CannabinoidsandTaste/flavor
• Themouthisapartofthebody• Cri?calroleindiet/nutri?on/sustenanceandQOL• Receptors&mechanismofac?onarebecomingbenerunderstood,
but,manymoreques?onsthananswers• Controlledtreatment&prophylac?cstudiesindicatedwith
pharmaceu?calproduct• Improvedcontrolofpa?entvariablesneeded• Delivery,dose,route,scheduleofcannabinoidstobedetermined• Validatedtoolsfororalcondi?on,oralhygiene,drymouth,taste,
smell,PROsneeded
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