Use of Psilocybin in End of Life Anxiety...

ShroomTherapyUseofPsilocybininEndofLife

AnxietyTreatment

KarolinaGrzesiak,PharmDPGY1PharmacyPracCceResident

CentralTexasVeteransHealthCareSystem

PharmacotherapyRoundsNovember17th2017

Objec;ves2

¨  ReviewendoflifeanxietyandAmericanSocietyofClinicalOncologytreatmentguidelines

¨  Outlinethehistoryandpharmacologyofpsilocybin

¨  Explorethephysiologicalandpsychologicaleffectsofpsilocybinonhealthyindividuals

¨  Evaluateliteraturedescribinguseofpsilocybinforendoflifeanxiety

¨  Discussfuturedirec;onfortreatmentwithhallucinogens

Pa;entCase3

“Iamsoanxiousthatitishardtothinkaboutanythingelse.Ihadlostmyfaithbecauseofanxietyanditisterrifying.”ALisa53yearoldwomanwithadiagnosisofmetasta;covariancancer.Pa;entiscurrentlyreceivingpallia;vetreatmentforpainandnausea.Shehasbeensufferingfromanxietyanddepressionsinceherdiagnosis3monthsago.Currentmedica;ons:MorphineER60mgdailyMorphineIR10mgthree;mesdailyPRNOndansetron4mgODTevery8hoursPRNSertraline150mgdailyBuspirone20mgthree;medailyTrazodone150mgatbed;meAlprazolam0.5mgthree;mesdailyPRNGabapen;n800mgthree;mesdaily

Isthispa;entagoodcandidateforPsilocybintherapy?

EndofLifeAnxiety

EndofLife

hWps://www.cancer.org

¨  Endoflifecare–careforterminallyillpatentsfocusedonimprovingqualityoflifeandmakingthemmorecomfortable

¨  Endoflifeemo;ons

Fear Anger Guiltandregret Grief

Anxiety Depression Feelingalone Seekingmeaning

Epidemiology

JPainSymptomManage.2011;42(5):691-701.

¨  Inpallia;vecare,anxietydisordersaffectapproximately10%ofpa;ents¤  Morecommoninwomen,physicallyimpaired,youngerpa;ents¤  Symptomsarereportedby25-48%ofadvancedcancerpa;ents

¨  Mul;factorialcausesofanxiety¤  Treatmentprocess¤  Diseaseprogression¤  Uncontrolledpain¤  Dying¤  Uncertainty

AmericanSocietyofClinicalOncologyGuidelines

JOncolPract.2015;11(2):133-4.

¨  Allpa;entswithcancerareevaluatedforsymptomsofdepressionandanxietyperiodicallyacrossthetrajectoryofcare

7itemGAD-7

None/mildsymptoms0-4,5-9

Offerreferraltosuppor;vecareservices

Moderatesymptoms10-14

Psychosocial,Psychologicalinterven;ons,±Pharmacologic

Severesymptoms15-21

CBT,Pharmacologic,combined

Pharmacological(SSRI,anxioly;cs)

Suppor;veCare

Psychosocial(group)

Psychological(individual)

PsilocybinOverview

AddictBiol.2002;7(4):357-64.

¨  IsolatedfromCentralAmericanmushroom(Psilocybemexicana)byaSwisschemistAlbertHofmannin1957¤ Foundinmanyspeciesofmushroomsworldwide

n Psilocybe,Conocybe,Gymnopilus,Panaeolus,andStropharian Alongwithpeyoteanddimethyltryptamine,psilocybinhasalonghistoryofceremonialuse

¨  Producedsynthe;callyin1958¤  Indocybin®Sandoz

n Puresynthe;cpsilocybinn Marketedforexperimentaluse

PsilocybinHistory

PsilocybinPharmacology

AddictBiol.2002;7(4):357-64.

¨  Hallucinogenicalkaloid¤  4-phosphoryloxy-N,N-dimethyltryptamine¤  Similarchemicalstructuretoserotonin

¨  Metabolizedto4metabolites(psilocin,4H1A,41-IIAA,41-IT)¤  Highlypotentagonistatserotonin5-HT2A¤  50%oralabsorp;on¤  Detectableinplasmain20-40minaheroraladministra;on¤  T½=163±64minwithPOadministra;on

¨  Considered30xstrongerthanmescaline,1/100-150aspotentasLSD¤  Stronglyvisual,lessemo;onallyintense,lesslikelytoresult

inparanoia

PhysiologicalandPsychologicalEffects11

¨  Eighthealthyvolunteerspar;cipatedinadouble-blind,placebo-controlled,dose-effectstudy

¨  Doses:¤  Verylowdose(VLD)45mcg/kg¤  Lowdose(LD)115mcg/kg¤  Mediumdose(MD)215mcg/kg¤  Highdose(HD)315mcg/kg

¨  BP,EKG,temperature,neuroendocrinedata,bloodchemistry

¨  GlobalAlteredStateofConsciousnessScore

AddictBiol.2002;7(4):357-64.Psychopharmacology(Berl).2004;172(2):145-56.

PhysiologicalEffects

¨  EKG¤ NoevidenceofPsilocybininducedchangeofcardiacelectrophysiology

¨  Bloodpressure¤  Increasedbloodpressureisapparentat60-90min

¨  Temperature¤ Nosignificantchanges

PhysiologicalEffects

¨  Neuroendocrinedata¤  TSH,prolac;n,ACTH,andcor;sollevelswereincreasedatt+105min,returnedbacktobaselineatt+300min

¨  Bloodchemistry¤  Athighdoses,liverfunc;ontests(GGTandAST)wereelevatedatt+105minandreturnedtonormalatt+300

PsychologicalEffects

¨  Serotoninreceptors(5-HT)playanimportantroleinpercep;on,affectregula;on,andaWen;on

¨  Dosesbetween45-315mcg/kgareclearlyratedaspsychoac;ve¤ Dosedependentchangesinmood,sensorypercep;on,aswellas;me,space,andselfpercep;on

¤  Effectslastabout3to6hours

LiteratureReview

SymptomScales

ArchGenPsychiatry.2011;68(1):71-8.JPsychopharmacol(Oxford).2016;30(12):1165-1180.JPsychopharmacol(Oxford).2016;30(12):1181-1197.

¨  BeckDepressionInventory(BDI)¤  Seriesofques;onsdevelopedtomeasuretheintensity,severity,anddepthof

depression¨  HospitalAnxietyandDepressionScale(HADS)

¤  Commonlyusedbydoctorstodeterminelevelsofanxietyanddepressionthatapa;entisexperiencing

¨  State-TraitAnxietyInventory(STAI)¤  Self-reportedassessmentofanxiety,differen;atesbetweenthetemporary

condi;onofstateanxietyandthemoregeneralandlong-standingqualityoftraitanxiety

¨  HamiltonAnxiety/DepressionRaCngScale(HAM-A,HAM-D)¤  Clinicianratedscalestoassessseverityofanxiety/depression

¨  ProfileofMoodStates¨  BriefPsychiatricRa;ngScale¨  5-DimensionAlteredStatesofConsciousnessProfile

GrobCS,DanforthAL,ChopraGS,etal(2011)

PilotStudyofPsilocybinTreatmentforAnxietyinPa;entswithAdvancedStageCancer

Grob,etal(2011)

ArchGenPsychiatry.2011;68(1):71-8.

• Toexplorethesafetyandefficacyofpsilocybininpa;entswithadvanced-stagecancerandreac;veanxiety

Objec;ve

• Double-blind,placebo-controlledstudy• CrossoverdesignDesign

• Psilocybin0.2mg/kg• Placebo(niacin250mg)Interven;on

Grob,etal(2011)

Inclusion

•  Advancedstage-cancer

•  DSM-IVdiagnosisofacutestressdisorderduetocanceroradjustmentdisorderwithanxietyExclusion

•  Centralnervoussysteminvolvementofthecancer

•  SevereCVillness•  Abnormalhepa;candrenalfunc;on

•  Diabetes•  Life;mehistoryofschizophrenia,bipolardisease,otherpsychiatricillness

•  Anxietyofaffec;vedisorderwithin1yearpriortocancerdiagnosis

•  Contraindicatedmedica;ons En

dpoints

•  Primary:•  Safetyandsubjectexperience

•  BeckDepressionInventory(BDI)

•  ProfileofMoodStates(POMS)

•  State-TraitAnxietyInventory(STAI)

•  AddiConal:•  5-DimensionAlteredStatesofConsciousnessprofile(5D-ASC)

•  BriefPsychiatricRa;ngScale

Grob,etal(2011)

12subjects(11women,36to58yearsold)

4breastcancer

3coloncancer

2ovariancancer

1salivaryglandcancer

1peritonealcancer

1mul;plemyeloma

12par;cipants3mo 11par;cipants4mo 8par;cipants6mo

Grob,etal(2011)

BDI,POMS,STAI

POMS,STAI,5D-ASC,BriefPsychiatricRaCngScale

BDI,POMS,STAI

Day-1 Day0 Day+1 Day+14 Monthly

BDI–BeckDepressionInventoryPOMS–ProfileofMoodStatesSTAI–State-TraitAnxietyInventory5D-ASC–5-DimensionAlteredStateOfConsciousnessProfile

Grob,etal(2011)

5-DimensionAlteredStateofConsciousnessProfile

OceanicBoundlessness

AnxiousEgoDissolu;on

VisionaryRestructuraliza;on

Grob,etal(2011)

Summary¨  Safephysiologicallyandpsychologically¨  ProfileofMoodStates

¤  Improvementduring2weeksposttreatment¨  BeckDepressionInventory

¤  Significantimprovementat6mo¨  State-TraitAnxietyInventory

¤  Downwardtrendintraitanxiety

LimitaCons¨  Smallsamplesize¨  Notgeneralizablepopula;on¨  Treatmentorderapparenttopar;cipants

RossS,BossisA,GussJ,etal(2016)

RapidandSustainedSymptomReduc;onFollowingPsilocybinTreatmentforAnxietyandDepressioninPa;entswithLife-ThreateningCancer:ARandomizedControlledTrial

Ross,etal(2016)

JPsychopharmacol(Oxford).2016;30(12):1165-1180.

•  Todetermineifpsilocybininconjunc;onwithtargetedpsychotherapywouldsignificantlydecreaseanxietyanddepressionsymptomsinpa;entswithlife-threateningcancerdiagnosis.

Objec;ve

• Double-blind,randomized,controlledstudy• CrossoverdesignDesign

•  Psilocybin0.3mg/kg•  Placebo(Niacin250mg)Interven;on

Ross,etal(2016)

Inclusion

•  18to76yearsold•  Projectedlifeexpectancyofatleast1year

•  Terminalcancerdiagnosis

•  PrimarydiagnosisofAcuteStressDisorder,GAD,AnxietyDisorderduetocancer,AdjustmentDisorderwithAnxiety+/-Depression

Exclusion

•  HADS<8•  Epilepsy,renaldisease,diabetes,abnormalliverfunc;on,severeCVdisease

•  Personalorimmediatefamilyhistoryofschizophrenia,bipolardisorder,delusionaldisorder,paranoiddisorder,orschizoaffec;vedisorder

•  Currentsubstanceusedisorder

•  Primary:•  HospitalAnxietyandDepressionScale(HADS)

•  AddiConal:•  Cardiovascularmeasures(HR,BP)

•  Adverseevents

Ross,etal(2016)

31subjects(90%Caucasian,62%women)

31%breastcancer

28%reproduc;ve

cancer17%GIcancer 14%hematologic

cancer 10%other

29subjects

28subjects6wk 26

subjectsDose2

24subjects6wk 23

subjects6mo

Ross,etal(2016)

AE,BP/HR,Depression/Anxiety

AE,Depression/Anxiety

AE,BP/HR

Baseline Dose1 Dose2Day1,2weeks,6weeks,Day-1

Day1,6weeks,26weeks

Psychotherapy PsychotherapyPsychotherapy

Ross,etal(2016)

Summary¨  Robust,rapid,andlong-las;nganxioly;candan;-depressanteffectsinpa;ents¤ At7weekssustainedreduc;oninBDI,HADS,STAI

LimitaCons¨  Crossoverdesign¨  Psilocybinorpsychotherapy¨  Samplesize,lackofgeneralizability

GriffithsRR,JohnsonMW,CarducciMA,etal(2016)

PsilocybinProducesSubstan;alandSustainedDecreasesinDepressionandAnxietyinPa;entwithLife-ThreateningCancer:ARandomizedDouble-BlindTrial

Griffiths,etal(2016)

• Todeterminetheefficacyofaclassichallucinogenfortreatmentofdepressedmoodandanxietyinpsychologicallydistressedcancerpa;ents.

Objec;ve

• Double-blind,randomized,controlledstudy • CrossoverdesignDesign

• Psilocybinhighdose(22or30mg/70kg)• Psilocybinlowdose(1or3mg/70kg)Interven;on

Inclusion

•  21to80yearsold•  Life-threateningcancerdiagnosis

•  DSM-IVdiagnosisthatincluded:GAD,AcuteStressDisorder,PTSD,MDD,DysthymicDisorder,AdjustmentDisorderwithanxiety

Exclusion

•  CancerwithknownCNSinvolvement

•  Hepa;cdysfunc;on•  CVcondi;ons(HTN,anginaAfib,TIA,stroke)

•  Epilepsy,Renalinsufficiency,Insulin-dependentdiabetes

•  Currentpsychoac;vemedica;ons

•  Potentmetabolicinducersorinhibitors

•  Psychiatricexclusions

•  Primary:•  HamiltonDepression/AnxietyRa;ngScale(HAM-Dand-A)

•  HospitalAnxietyandDepressionScale(HADS)

•  AddiConal:•  Cardiovascularmeasures

•  Adverseeffects

51subjects(94%Caucasian,49%

women)

13breastcancer

7aerodiges;vecancer 4GIcancer

18genitourinary

cancer8hematologicmalignancies 1othercancer

51subjects

49subjects

46subjects6mo

Griffiths,etal(2016)39

AnxietyDepression

BP/HR,AE

AnxietyDepression

BP/HR,AE

AnxietyDepression

Baseline Dose1 5weeks Dose2 5weeks 6months

StarsymbolindicatesasignificantdifferencebetweenthetwogroupsatthePost-session1;me-point(p<0.05,plannedcomparison).CrosssymbolindicatesasignificantdifferencebetweenthePost-session1andPost-session2;me-pointsintheLow-Dose-1st(High-Dose-2nd)Group(p<0.05,plannedcomparison).

Summary¨  Longtermclinicalresponsetotreatment(83%)at6months

¨  Pa;entsexpectedpsilocybinboth;mes,lessexpectancyeffects

¨  HigherincidenceofadverseeffectsLimitaCons¨  Notdiversepopula;on

¤  >90%Caucasian,collegeorpost-graduateeduca;on¨  Crossoverdesign

SummaryandConclusion

Summary46

Grobetal(2011) Rossetal(2016) Griffithsetal(2016)

Psilocybin0.2mg/kgNiacin250mg

Psilocybin0.3mg/kgNiacin250mg

Psilocybin0.3or0.4mg/kgPsilocybin0.01or0.04mg/kg

12cancerpa;ents 31cancerpa;ents 51cancerpa;ents

6monthfollow-up 6monthfollow-up 6monthfollow-up

Briefcontacttocheck-induringsession

Professionalpsychotherapypreandpostsession

Sessionmonitors,introducedpresession

STAI–trendBDI–6monthssignificant

improvement

7weekssustainedreduc;oninBDI,HADS,STAI

6monthclinicalsignificantresponse(83%HAM-A)

Presenter’sConclusion47

¨  Psilocybinissafetouseinaverynarrowpa;entpopula;onwithendoflifeanxiety¤ Endorgandamage¤ Serotonergicdrugs¤ Chronicdiseases

¨  Notenoughsafetyandefficacydatatouseasstandardofcare

¨  Inconsistentstudydesigncreatesbiasedresults

Pa;entCase48

“Iamsoanxiousthatitishardtothinkaboutanythingelse.Ihadlostmyfaithbecauseofanxietyanditisterrifying.”

ALisa53yearoldwomanwithadiagnosisofmetasta;covariancancer.Pa;entiscurrentlyreceivingpallia;vetreatmentforpainandnausea.Shehasbeensufferingfromanxietyanddepressionsinceherdiagnosis3monthsago.

Isthispa;entagoodcandidateforPsilocybintherapy?

FutureDirec;on49

¨  Promisingresultswarrantaneedforfurtherinves;ga;on¤  Larger,morediversepopula;on¤  Studydesign

¨  Exploringotherhallucinogenicdrugsandtheirpoten;almedicaluse¤ MDMAforPTSD¤  Psilocybinfortreatment-resistantdepressionandanxiety

¨  Gran;ngaccesstoScheduleIdrugsforresearchandmedicaluse

Acknowledgment50

¨  Evaluator:TroyMoore,PharmD,MSPharm,BCPP

¨  StephenSaklad,PharmD,BCPP¨  KaterineGetchell,PharmD,BCACP¨  CTVHCSCo-ResidentsandPreceptors

References

¨  AmericanCancerSociety.Emo;onsasyouneartheend.Availableat:hWps://www.cancer.org/treatment/end-of-life-care/nearing-the-end-of-life/emo;ons.html.AccessedOctober12th2017.

¨  AndersenBL,RowlandJH,SomerfieldMR.Screening,assessment,andcareofanxietyanddepressivesymptomsinadultswithcancer:anAmericansocietyofclinicaloncologyguidelineadapta;on.JOncolPract.2015;11(2):133-4.

¨  GriffithsRR,JohnsonMW,CarducciMA,etal.Psilocybinproducessubstan;alandsustaineddecreasesindepressionandanxietyinpa;entswithlife-threateningcancer:Arandomizeddouble-blindtrial.JPsychopharmacol(Oxford).2016;30(12):1181-1197.

¨  GrobC.S.,BossisA.P.,GriffithsR.R.(2013)UseoftheClassicHallucinogenPsilocybinforTreatmentofExisten;alDistressAssociatedwithCancer.In:CarrB.,STEELJ.(eds)PsychologicalAspectsofCancer.Springer,Boston,MA

¨  GrobCS,DanforthAL,ChopraGS,etal.Pilotstudyofpsilocybintreatmentforanxietyinpa;entswithadvanced-stagecancer.ArchGenPsychiatry.2011;68(1):71-8.

¨  HaslerF,GrimbergU,BenzMA,HuberT,VollenweiderFX.Acutepsychologicalandphysiologicaleffectsofpsilocybininhealthyhumans:adouble-blind,placebo-controlleddose-effectstudy.Psychopharmacology(Berl).2004;172(2):145-56.

¨  KolvaE,RosenfeldB,PessinH,BreitbartW,BresciaR.Anxietyinterminallyillcancerpa;ents.JPainSymptomManage.2011;42(5):691-701.

¨  Na;onalCancerIns;tute.Pallia;veCareinCancer.AvailableathWps://www.cancer.gov/about-cancer/advanced-cancer/care-choices/pallia;ve-care-fact-sheet#q1.AccessedOctober12th2017.

¨  Na;onalCancerIns;tute.HospiceCare.AvailableathWps://www.cancer.gov/about-cancer/advanced-cancer/care-choices/hospice-fact-sheet.AccessedOctober12th2017.

¨  PassieT,SeifertJ,SchneiderU,EmrichHM.Thepharmacologyofpsilocybin.AddictBiol.2002;7(4):357-64.

¨  RossS,BossisA,GussJ,etal.Rapidandsustainedsymptomreduc;onfollowingpsilocybintreatmentforanxietyanddepressioninpa;entswithlife-threateningcancer:arandomizedcontrolledtrial.JPsychopharmacol(Oxford).2016;30(12):1165-1180.

ShroomTherapyUseofPsilocybininEndofLife

AnxietyTreatment

KarolinaGrzesiak,PharmDPGY1PharmacyPracCceResident

CentralTexasVeteransHealthCareSystem

PharmacotherapyRoundsNovember17th2017

Use of Psilocybin in End of Life Anxiety...

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