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DangerousFantasyorRisingStar?ReviewofNaltrexoneforopiate,alcohol,and

stimulantusedisorders.

Katherine Grieco, DOChief of Addiction Medicine St. Elizabeth’s Medical CenterAssistant Clinical Professor, Tufts University School of Medicine 12/17

Ihavenothingtodisclose

Outline

• Briefupdateonopioidepidemic– Currentfentanylstatistics– NewNarcan efficacydata

• Emergingnon-narcoticRxdrugsofabuse• Naltrexone

• opiateuse• EtOH use• methamphetamineuse

PresidentTrump’s Commission onCombatingtheOpioidEpidemic

11/1/17

• Drugcourtsinallfederaljudicialdistricts

• Streamlinefederalfundingopportunities

• Changestoreimbursementratessetbyfederaladdictiontreatmentproviders

• AllowmoreEMSresponderstoadministernaloxone

• Tightenrequirementsforprescribers

• Eliminatingpatientpainevaluationsfromsurveys- CMS

• Stepstoensureparity• Betterdataonoverdosedeaths• Bolsteringresearchmoney

Positive feedback from various professional organizations; attacking issue at all angles.

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CDC:Fentanyl Deathsin2016:Up540%in3Years(provisionaldata)

20002015

Increase in deaths from Cocaine & meth use (often involve opiates)

Deaths involving synthetic opioids, mostly fentanyl, jumped from 3,000 to 20,000 in 3 yrs.

ProfitforTraffickers• 1kilogramofFentanylcosts$2,000-$3000

(vs1kgheroin$90,000)

Cutting supply does not stop addiction.

US Customs and Border Protection: Currently seizing pill presses at a rate 19 times higher than in 2011.

Port of Long Beach, California

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Question:Canyouspotthefake??

A. B.

Courtesy of California Poison Control, San Francisco DivisionHydrocodone vs fentanyl/promethazine/cocaine

Fentanyl- California• Overdoses,deathsverylowinCA• 6/10/17:SanYsidroportofentry,U.S.CustomsandBorderProtectionofficialsmadeafentanylseizurethatsetarecordfortheU.S.-Mexicoborder.

• 6/19/17:oneofthenation’slargestfentanylseizuresinLemonGrove,SanDiego

NarcanEfficacyStudy• AmericanCollegeofEmergencyPhysiciansConf,10/30/17

– B&WHospital,S.Weiner• MassachusettsDepartmentofHealth

– ambulance,hospital,anddeathrecords– 12,192peopleadministerednaloxonebyEMS;7/1/13thru12/31/15

• 93%survivedtheoverdose– 6.5%diedthedaytheyreceivedthemedication.

• Ofthosewhosurvived,9.9%diedwithinayear.– Medianagewas54.

• Ofthosewhodied,40%didsooutsideofthehospitalandmorethanhalfpassedawayinthefirstmonth.

• “Youhavea1in10chanceofdyingifwedon’tgetyouintotreatment.”

OtherRxDrugsofAbuse/Cocktails

• Gabapentin– nextslide• Pregabalin

• Controlledsubstance,ScheduleV• Clonidine

– SimilartoBZDhigh• Promethazine

– Oftenusedinconjunctionw/opiatesforeuphoria• Loperamide

– Highdosescancauseeuphoria– Serioussideeffects

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Gabapentin

• Controlledsubstance,scheduleV– Kentuckyisthefirststate– SeveralstatesnowreportonPMP– 9/17:2nd mostcommonlyprescribedpainmedication.

• Gabapentin,opioids,andtheriskofopioid-relateddeath:Apopulation-basednestedcase-controlstudy- TGomesetal,PLoS 10/3/2017

– Canada,1997– 2013– Casesdefinedasopioiduserswhodiedofanopioid-relatedcause

• Concomitantgabapentinandopioidexposure– associatedwitha49%higherriskofdyingfromanopioidoverdose– Seenw/moderate(900- 1,799mgdaily)andhigh(>1,800mgdaily)gabapentindoses

Naltrexone

Question• WhichofthefollowingstatementsisTRUEaboutnaltrexone?a)FDAapprovedforbothalcohol&opioidusedisorders.b)FDAapprovedforalcohol&opioidusedisorder,andmostrecentlystimulantusedisorder(crystalmeth).

c)FDAapprovedforalcoholusedisorder,butnotforopiateusedisorder.

d)Therearerobuststudiesshowingefficacyofnaltrexoneinalcohol,opiates,andcrystalmethuse.

CaseStudy• 28yo malewithHIV,HCV,severeopiateusedisorder,mildalcoholusedisorder.

• Bupe maintenancefor4months(weeklyRxs),relapsed• stoppedtakingonsomedayssohecouldgethigh.

• Nohistoryofmethadonemaintenance– interfereswithwork• Usingheroin/fentanylillicitly,EtOH for2months,occas streetbupetoavoidw/d.Hashad3overdoses,mostrecently10/17.

• Askingaboutnaltrexone,“Iwantthatshot.”– HIVwellcontrolledwithmeds- Dolutegravir plustenofovir/emtricitabine– HCVuntreated,stable– Bipolar,PTSD- Lamictal,prazosin

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MATforOpiateUseDisorder– OptionsBuprenorphine/naloxone– 1st• Partialopioidagonist• Ceilingeffect– resp depression,

sedation• Films/Pills/Injectable• Officebasedtx• Stablepts– nopolydruguse,

supportsysteminplace,psychiatricallystable

• MUSTbeinwithdrawaltostart• Robustdatatosupportefficacy

Methadonemaintenance(MMTP)– 1st• Fullopioidagonist• HigherriskforOD,sedation• Liquidform,dailydosing• FederallyqualifiedOTP(opiatetx

program)• Highlyregulated,structure• Counselingmandated• Ptsinneedofmonitoring,lackof

supportsystem,psychiatricallyunstable,Failedbupe

• Withdrawalnotnecessarytostart• Robustdatatosupportefficacy

Naltrexone– 2nd• Opioidblocker• NOriskforODfromNal;risk

tryingtooverrideblockade• Pillorinjection(Vivitrol)• Officebased• Ptsw/cravings,notexperiencing

withdrawal,notcurrentlyusing• Stablepts- nopolydruguse,

supportsysteminplace,psychiatricallystable(?forptswhohavefailedMMTP/bupe)

• MUSTbeinwithdrawaltostart• Limiteddata

Opiatereplacementtreatmentisassociatedwithreducedmortality,lowerHIVtransmission,improvedsocialfunctioning,andreducedcriminalbehavior.

Naltrexone• Notanewdrug,but–

• increaseinmarketingforOUD:“non-addictivemedication”• gaininginterestfrompatients

• FDAapprovedforOUD,NOT1st line• FDAapprovedforAUD,1st line• NotFDAapprovedforotherSUDs

• FDAapprovedforweightloss:Contrave (nal/buproprion)• Offlabelforself-injuriousbehavior

• Oralformulation– dailydosing• Extendedrelease

– Injection:monthly– Implant:2months(notFDAapproved)

NaltrexoneforOUD• OpiateUseDisorder– approved2010• Mu- opiatereceptorantagonist

– Blocksexogenousopiates;blocksendogenousopiatepeptides– preventtheincreaseddopaminereleaseà pleasurablereinforcingeffectsofdrugs

• Clinically:– Helpwithcravings– Relapseprevention

• Oralformulation(50mgdaily):pooradherence,highdropoutrate,increasedmortality

• InjectableXR(monthly):decentamountofstudieshaveshownefficacyvsplacebo/TAU(HIVandnon-HIVpts)• Incarceration– datasupportinguse;methadone/bupe notoptions

NaltrexoneTrialsforOUD• FDAapprovedbasedonRussianstudy,2011

– Injectable extended-releasenaltrexoneforopioiddependence:adouble-blind,placebo-controlled,multicentre randomised trial.– EKrupitsky,Lancet2011

– Nofollowupdatare:overdoseafterstoppingthemedication

• AustralianStudies,2013– Excessmortalityamongopioid-usingpatientstreatedwithoralnaltrexoneinAustralia.- LDegenhardt,DrugAlcoholRev2013

– Totaloralnaltrexonemortalitywassignificantlygreatervsmethadone• Highmortalityrateposttreatmentcessation.

• FewstudiescomparingXRtobuprenorphine/naloxoneormethadone(nonespecificallyinHIV)

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XRNaltrexonevsBuprenorphineJAMAPsychiatry10/18/17

Open-label,randomizedclinicaltrialx12wksN=159,(Norway)

PrimaryOutcomes

– Retentioninstudy– #ofUDTsnegativeforillicitopiates– #ofdaysofheroin/illicitopiateuse

SecondaryOutcomes

– #ofdaysofTHC,amphet,cocaine,BZDs,EtOH

– #ofdaysofinjecting– #degreeofopiatecravings– Life/treatmentsatisfaction– Mentalhealth

XRNaltrexonevsBuprenorphine• Noninferior tobuprenorphine/naloxone

– Primaryoutcomeresults:• retentionrate• #negUDTs• #daysofOPIuse

– Secondaryoutcomeresults:• significantlylessheroincraving• significantreductioninBZDuse• significantlyhigherlife/treatmentsatisfaction

• CanweextrapolatethistoUSpopulation?

–Enrollmentfolloweddetox–Avg buprenorphinedose~11mg–Nofollowupdatare:overdoseafterstoppingthemedication

Inthepipeline…XRNaltrexonevsBuprenorphine

• NYUStudy:N=600,6-monthtrial• XRNalvsbuprenorphine/nal• completed1/2017• Resultsnotpublishedyet…

ReturntoCaseStudy• 28yo malewithHIV,HCV,severeopiateusedisorder,mildalcoholusedisorder.

• Bupe maintenancefor4months(weeklyRxs),relapsed• stoppedtakingonsomedayssohecouldgethigh.

• Nohistoryofmethadonemaintenance– interfereswithwork• Usingheroin/fentanylillicitly,EtOH for2months,occas streetbupetoavoidw/d.Hashad3overdoses,mostrecently10/17.

• Askingaboutnaltrexone,“Iwanttheshot.”– HIVwellcontrolledwithmeds- Dolutegravir plustenofovir/emtricitabine– HCVuntreated,stable– Bipolar,PTSD- Lamictal,prazosin

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XRNaltrexoneGuidelines• SAMHSA - ClinicalUseofExtended-ReleaseInjectableNaltrexoneinthetreatmentofOUD:ABriefGuide

• Officebasedaddictiontx– KEY:Comprehensivetxapproach

• Counseling• Psychiatrictreatmentasneeded• Socialsupport:AA,NA,mutual-helpprograms

IdealCandidates• S/popiatedetoxification

– Nowithdrawalsxs– Co-occurringalcoholusedisorder– Shortorlesssevereaddictionhistory– Highlymotivated:

• Professionalsdemonstratesobrietytolicensingboards,criminaljusticeofficials– HCP,attorneys,pilots

• Agonisttherapyforprofessionalsisbannedinsomestates– Unsuccessfultx withbuprenorphineormethadone

• Dependsonreasonforfailure– Successfultx withagonist– butwouldlike‘morefreedom’

NotIdealCandidates

• Unabletocomplete/toleratew/d• PAWS:postacutewithdrawalsyndrome – seenextslide• Unstablepsychiatricsxs• Chronicpainwhichrequiresopioidtx• Advancedliverdisease,impendingliverfailure,acutehep

– ToleratedinstablechronicHBV,HCV,elevatedLFTs

Post-acutewithdrawalsyndrome(PAWS)• 4-8weeksafterdetox;maylast6-12months• Lessphysicalsxs,morepsychologicalsxs

– Insomnia,irritability,anxiety,moodchanges,memoryissues,anhedonia– SeenBZDs,EtOH,OPI,stimulants

• Impairmentinreversallearning“WHENIUSEDRUGSIFEELGOOD”

needstochangeto“WHENIUSEDRUGSBADTHINGSHAPPEN”

– Inabilitytoadapttonewunderstanding– Involvesdopamineandglutamate

• LackofevidencetosupportDSM-5diagnosis

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Contraindications/Warnings• Ptsreceivinglongterm opioidtherapy• Activelytakingbuprenorphineormethadone• Sensitivitytocomponentsofdiluent

– polylactide-co-glycolide,carboxymethylcellulose• BodymassprecludesIMinjectionwith2-inchneedle• ISR– injectionsitereactions• Caution

– activeliverdx,mod-to-severerenalimpairment– Thrombocytopenia,coagulationdisorder– PregnancycategoryC;breastfeeding

Contraindications/Warnings

• Hypersensitivityreactions• Hepatotoxicity• Depression/suicidality– relative• Precipitatedopioidwithdrawal

– Moreseverethannaturalwithdrawal

• Overdosemayresultfromtryingtoovercometheopiateblockade

Warning:OpioidOverdose

• Nocomprehensivemortalitydatayetavailableforinjectable• Casesoffatalopioidoverdosehavebeenreportedinptswho:

– Usedopioidsatorneartheendofthe1-monthdosinginterval.– Usedopioidsaftermissingadose– Attemptedtoovercometheopioidblockade– Upregulationofopioidreceptorsincreasessensitivitytoopiateeffects

• 1/3ofptswill“test”blockade,within1-2daysafter1st injection• Veryfewpatientstrytointentionally“overridetheblockade”

Sideeffects• 2%:LFTabnormalities• 4-7%:nausea,vomiting,headache,fatigue,andmusclecramps• 5%:Psych- depression,suicidalthoughtsand/orbehavior

• OUDsuiciderisk:10%vs1.3%inthegenpopulation• OralNal:10%suicidality

• Injectionsitepainandinduration– Asepticabscess,obesity– subcutaneousfat

• Seriousallergicreactions:skinrash,facialortongueswelling• Rarecasesofsevereallergicpneumonia(eosinophilic)

• Majorityofsideeffectswerereportedas“mildtomoderate”.• NosignificantinteractionswithHIVmeds

• Liver

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SafetyProfile:NaltrexoneinHIV• HepaticsafetyandantiretroviraleffectivenessinHIV-infectedpatientsreceivingnaltrexone– JTetrault,etal.2/2012,Alcoholism,Clinical&ExperimentalResearch.– Oralformulation– proventobesafeinHIV,HIVRNAdecreased

• AnevaluationofhepaticenzymeelevationsamongHIV-infectedreleasedprisonersenrolledintworandomizedplacebo-controlledtrialsofextendedreleasenaltrexone– PVagenas,7/2014,JSubstanceAbuseTx– XRformulation– nodifferenceinLFTelevationvsplacebo– 50%ofpts+HCV– 33%onpsychiatricmedication

SafetyProfile:NaltrexoneHIV,HCV

• Hepaticsafetyofinjectableextended-releasenaltrexoneinpatientswithchronichepatitisCandHIVinfection.- MCMitchell,11/2012,JStudAlcoholDrugs.

– 88%HIV+,42%HCV+– Safetouse

• Feasibilityandsafetyofextended-releasenaltrexonetreatmentofopioidandalcoholusedisorderinHIVclinics:apilot/feasibilityrandomizedtrial.– PTKorthuis,PLum etal,6/2017Addiction.– Non-blindedrandomizedtrialofXR-NTXvspharmacotherapyTAU,N=51– Ptsw/OUD:HIVsuppressionimprovedfrom67to80%forXR-NTX– feasible&safe

Plasmaconcentrationsonadailybasisx1month

– XRNal remainsrelativelystablebythefifthdayofthemonth– concentrationoforalnal peaksonadailybasis.

• overaperiodof24hours,oralnal peakswithinthefirsthourofdosingandfallsbelowtherapeuticlevelswithin8hours.

RedLine:XRNalYellowLine:oralnal

XRNaltrexone

• 380mgIMinjection• Glutealmuscleevery28-30days• 2peaklevelsfollowinginjection

– 2hoursafter– 2-3dayslater

• After14days,bloodlevelslowlydeclinesinlinearfashion• Reachsteadystateattheendofthefirstdosinginterval

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HowtoPrescribe(sameforOUD&AUD)

• Opiatefreefor7-10days– 2weeksforbupe ormethadone

• Screen– LFTS,renalfunctionthenQ6-12mos

• RecCheck3-4months• LFTsincreasemildandself-limiting,resolveswith

continuation– UDSw/ethylglucuronide,HCG

• ThenrandomUDS• CheckPMP

• Tolerancetest-POnaltrexonefor2wks– Someinsurancedictates30daytrialwith

compliancefailure• Challengetest(NAforAUD)

– Narcandoseand/orpo challengetest:25mgnaltrexone,wait1hour

• Injection:upperouterquadofglutealregion,alternatesidemonthly– Physician,Nurse,orPAcanadminister

• Housekeepingitems– Orderedviaspecialtypharmacy

– Deliveredtoclinic– Storedinfridge– F/umedicationmonitoringcanbe

billed/performedbyanRN.

Toleratingthe7-10dayopiate-freegap• Comfortmedications• Naltrexonedrivenwithdrawal

– Anesthesia-assistedrapidopioiddetoxNOTrecommendedperCDC• Naltrexoneplusgeneralanesthesia,BZDsover4-6hrs• Riskofpersistentw/dsxs,andriskofdeath

– Crosstaperofagonistwithnaltrexoneover7-10days,seenextslide

• TheBridgeDevice

TransitionfromdetoxtoXRNal

• Long-ActingInjectableNaltrexoneInduction:ARandomizedTrialofOutpatientOpioidDetoxificationWithNaltrexoneVersusBuprenorphine.MSullivan,etal.AmJPsychiatry5/17

– Bupetaperfollowedby7daysofopiatefreeperiod– Versusbupedosexone,thenascendingdosesofnaltrexoneandclonidinex7days

– NaldetoxgroupwasmorelikelytoreachinductionofXRnal

TheNeurostimSystem-2Bridge

• FDAapproved11/15/17foropiatew/dsymptoms– Approved2014foracupuncture

• Battery-operateddevice,attachestotheear• Transmitselectricalpulsesthroughfourpoints• Wearfor5days,reducessxs ofopiatew/d

• Singlearmclinicalstudy,n=73– COWSscoredecreasedinallptsby31%,30minafterplacement– 88%ofptstransitionedtoMAT“successfully”after5daysofusingdevice

• Contraindicated:hemophilia,cardiacpacemakers,psoriasisvulgaris• Rxonly• Nocontrolledclinicaltrial

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SpecialConsiderations• Acuteinjury/pain

– Non-opiateanalgesics– Acetaminophen/NSAIDs,NMDAantagonists(ex.Ketamine),Alpha-2agonists(ex.Clonidine),Antispasmotics (ex.Baclofen),Antineuropathic agents(ex.Gabapentin)

– Non-pharmacologictherapies:peripheralandneuraxial nerveblocks,localanesthesia

• Emergencysurgery:– regionalanesthesia,benzodiazepines,non-opiateanalgesics,ketamine– Opiateblockadecanbeoverridden– hospitalsetting

• Electivesurgery:– Oralnaltrexone:d/cuse72hoursprior;½life14hours(5half-lives)– XRNaltrexone:lastinjection4-6wks prior;½life5days– OR- transition

tooraltherapywithdiscontinuation3dayspreoperatively.

• Medicalalertbracelet

XRNaltrexoneinProfessionals

• Studiesshowsuccessinanesthesiologists• XRNal inHCPs,JournalofAddictionMedicine,6/2017

– Nurses,doctors,pharmacists– N=38,2years– Longesttx durationofanystudyofXRNal– 1st studyinHCPsofXRNal foropiateusedisorder– increasedmentalhealthfunctioning,increaseinemploymentrate,decreaseinopiatecravings

ReturntoCaseStudy• 28yo malewithHIV,HCV,severeopiateusedisorder,mildalcoholusedisorder.

• Bupe maintenancefor4months(weeklyRxs),relapsed• stoppedtakingonsomedayssohecouldgethigh.

• Nohistoryofmethadonemaintenance– interfereswithwork• Usingheroin/fentanylillicitly,EtOH for2months,occas streetbupetoavoidw/d.Hashad3overdoses,mostrecently10/17.

• Askingaboutnaltrexone,“Iwanttheshot.”– HIVwellcontrolledwithmeds- Dolutegravir plustenofovir/emtricitabine– HCVuntreated,stable– Bipolar,PTSD- Lamictal,prazosin

Question• Isourpatientagoodcandidateforinjectablenaltrexone?

• YES

• NO

• NOTSURE

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YesorNo?• Yes

– WouldhelpwithcravingsforbothOPIandEtOH– Longacting– notableto‘stop’inordertogethigh– Wouldassistinmaintainingemployment– Decliningtoconsiderbupe/methadone– Willengagept – ifhefails,canswitchto1st lineoptions

• No– Lackofstructurewithmonthlyinjection– RelapsedonanagonistwithweeklyRxs– Activelyusing– needstodetoxtostartNal (↑riskofoverdose)– Concernforworseningpsychsxs– Lackofevidence– NOT firstlinetreatment,considermethadone(1st line)

Summary– XRNalforOUD• XRNaltrexoneisstillconsidered2nd lineforOUDtx.• Morestudiesneededcomparingto1st lineofbupeandMMTP.

– It’sbetterthanplacebo– thisisallweknow.

• IfptfailedMMTPand/orbupe,bemorecautiousw/naltrexone.• Inthemidstofanopiatecrisis,consider:

– Engagement- meetingpatientswheretheyare– propereducationre:MAToptions,risksofOD– Weighingrisks/benefits

PROS

CONS

NaltrexoneforAlcoholUseDisorder

• SeveralRCTs:strongevidenceNalsignificantlyreduces– alcoholrelapses– frequencyandquantityofalcoholconsumptioninthosewhododrink– alcoholcravings

• Ptsshouldnotbeactivelydrinkingattimeofadministration– Considerdetoxfirst(dependsonseverityofusedisorder)

• DoesnotreactadverselywithEtOHintake• Sameprescribinginformation/processasforOUD

MATforAlcoholUseDisorder– OptionsDisulfiram(Antabuse)

–NegativeReinforcement,doesnotcontrolcravings–Ethanol-->Acetaldehyde-->Acetate–BuildupofAcetaldehyde

•Flushing,nausea•Headache/dizzy•Palpitations

•Dose:250mgdaily->500mgdaily•DrugInteractions

–Warfarin–Anti-convulsants/seizuremeds–HIVmeds– Ritonavir(oralsolution)

•SideEffects:hepatotoxicity,neuropathy•Contraindications

–Pregnancy–RecentEtOH use(LFTs,rxn)–CognitiveImpairment

Acamprosate (Campral)• Mitigates/modulateseffectsof

alcoholinthebrain• Efficacy??

-Reviewof7trials-Abstinentatoneyear:

Acamprosate:23%Placebo:15%

-COMBINEStudy:nosignificanteffectondrinkingvsplacebo

• 333mgtablets:2tablets3x/dayStartafterperiodofabstinenceDose666mgTID

• SE:bloating,diarrhea• Contraindications

- Renaldisease- Pregnancy

Naltrexone• Opioidantagonist• Pillorinjection(Vivitrol)• Officebased• Efficacy

–19publishedstudieshaveshownefficacyvsplacebo

• Dosage:–Oralform:50mgdaily–Injectableform:monthly

• SE:Nausea,headache,fatigue• Contraindications:

– Acuteliverdisease–Takingopioids

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MethamphetamineUse

MAUse

• HIVInSiteUCSF/Ward86PracticeRecommendations• Behavioraltherapies– THE onlyevidence-basedtreatment

– MatrixModel:CBT,recovery/relapse-preventiongroups,drugscreening

– StonewallProject:InSF

• NoFDAapprovedmedicationsfortreatment• Studies– naltrexone,psychostimulants

– Smallsize,highdropoutrate– Promisingbutnotcompelling

MA– 1st USNaltrexonestudy

• Neuropsychopharmacology,5/15– UCLA,LRayetal.

• N:30,OralNaltrexonevsPlacebo• Significantlyreducedrewardingeffectsofmeth

– Significantlyreducedcravings– Lessarousedbymeth

• N:25(subsetofabovestudy)• fMRIs:resultsnotpublishedyet

OralNaltrexoneinMA&EtOH• Feasibility,acceptability,andtolerabilityoftargetednaltrexonefornondependentmethamphetamine-usingandbinge-drinkingmenwhohavesexwithmen.JAcquir ImmuneDefic Syndr.2016,SantosGM,etal.

• 30non-dependentMA-use,binge-drinkingMSM• Nal vsplacebox8weeks• Targeteduse– craving,anticipatinguse• RESULTS

• Feasible,acceptable,andwelltolerated• Associatedw/significantsexualriskreductions• Forsome,associatedw/methandbinge-drinkingreductions.

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Incontrast…XRNalinMAuse

• Extended–releasenaltrexoneformethamphetaminedependenceamongmenwhohavesexwithmen:arandomizedplacebo-controlledtrial.POCoffinetal,Addiction2017.– Double-blind,placebo-controlled,randomizedtrialofXRNALversusplaceboover12 weeksfrom2012to2015.

– Extended-release naltrexone doesnotappeartoreduce methamphetamine useorsexualriskbehaviorsamongmethamphetamine-dependentMSMcomparedwithplacebo.

MA• MolecularPsychiatry,3/17;TheScrippsResearchInstitute• Rats:Ceasingmethtriggeredneurogenesisinthedentategyrus

– Strengtheneddrug-associatedmemories– Dentategyrusformsnewmemories

• Ratslearnedtoassociateaparticularlocationwithmethuse.

• Returningtothislocationservedasatriggeringcue.– intheory,promptingapt torelapse.

MA

• SyntheticmoleculeIsx-9(isoxazole-9) blocksneurogenesis– Ratslesslikelytorelapse– Needclinicaltrials

Summary

• Naltrexone– 1st lineforAUD– 2nd lineforOUD– needmoredata;usewithcaution– NotFDAapprovedforMA– needmoredata

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ThankYou

International OverdoseAwareness Day