Michigan Department of Community Health

Michigan Department 0f Community Health, Office of Drug Control Policy The Michigan Association of Community Mental Health March 27, 2009

NationalNational TrendsTrends andand DeterrentDeterrent StrategiesStrategies ForFor PrescriptionPrescription andand OTCOTC DrugDrug AbuseAbuse

Joseph Rannazzisi Deputy Assistant Administrator Office of Diversion Control Drug Enforcement Administration IntroductionIntroduction

BackgroundBackground andand StatisticsStatistics RegulatoryRegulatory ControlControl MethodsMethods ofof DiversionDiversion InternetInternet DiversionDiversion CommonlyCommonly DivertedDiverted PharmaceuticalsPharmaceuticals Steroids/Steroids/hGHhGH DietaryDietary SupplementsSupplements SalviaSalvia DivinorumDivinorum TheThe 19601960’’ss

Marijuana Seconal LSD

Dexedrine

Meprobamate TheThe 19701970’’ss

Heroin T’s and Blues 4’s and Doors (Talwin and Pyrabenzamine) TheThe 19801980’’ss Tylenol w/Codeine and Doriden

Hydromorphone Cocaine TheThe 19901990’’ss Oxycodone

Methamphetamine 20002000

Hydrocodone

Ketamine

Alprazolam

Flunitrazapam MDMA (Rohypnol) Scope and Extent of Problem 2004 2007

0.30.3 millionmillion 0.35 million SedativesSedatives

1.21.2 millionmillion 1.11.1 millionmillion StimulantsStimulants

1.61.6 millionmillion 1.81.8 millionmillion Anti-Anxiety Medication

4.44.4 millionmillion 5.25.2 millionmillion NarcoticNarcotic PainPain RelieversRelievers

Source: 2004 and 2007 National Survey on Drug Use and Health TeensTeens andand TheirTheir AttitudesAttitudes

1 in 5 teens report abusing Rx medications to get high 2 in 5 teens believe that Rx meds are “much safer” than illegal drugs 31% teens believe there’s “nothing wrong” with using Rx meds without a prescription “once in a while” Nearly 3 in 10 teens believe Rx pain relievers Partnership for a Drug Free America Study are not addictive RegulatoryRegulatory ControlControl Controlled Substances Act of 1970

• Established a “closed system” of distribution

• Five “schedules” of controlled substances

• Created the Compliance Program (1971) to monitor the legitimate manufacture and distribution of controlled substances

• Clearly differentiated controlled substances from other “legend” drugs handled under the FDCA

• Authorized DEA to register dispensers, practitioners and pharmacies

• CSA/Regulations address creation, signature, retention of prescription/records PrescriptionPrescription RequirementsRequirements Schedule II Schedule III Schedule IV Schedule V

Written Yes Yes Yes Yes

Oral Emergency Yes Yes Yes Only*

Facsimile Yes** Yes Yes Yes

Refills No Yes# Yes# Yes#

Partial Fills Yes*** Yes Yes Yes

* Must be reduced in writing, and followed by sign, hard copy of the prescription. ** A signed, hard copy of the prescription must be presented before the medication is dispensed. *** 72 hour time limitation. # With medical authorization, up to 5 in 6 months. PrescriptionPrescription DrugDrug MonitoringMonitoring ProgramsPrograms

BenefitsBenefits

TheThe PDMPPDMP databasedatabase allowsallows investigatorsinvestigators toto obtainobtain pharmacypharmacy datadata fromfrom multiplemultiple locationslocations withoutwithout havinghaving toto visitvisit eacheach andand everyevery pharmacy.pharmacy.

DeterDeter andand identifyidentify illegalillegal activityactivity suchsuch asas prescriptionprescription forgery,forgery, indiscriminateindiscriminate prescribingprescribing andand "doctor"doctor shopping."shopping."

PatientPatient specificspecific drugdrug informationinformation uponupon requestrequest ofof thethe patientpatient’’ss physicianphysician oror pharmacist.pharmacist.

NotificationNotification ofof physiciansphysicians whenwhen theirtheir patientspatients areare seeingseeing multiplemultiple prescribersprescribers forfor thethe samesame classclass ofof drugs.drugs.

AssistsAssists healthcarehealthcare professionalsprofessionals inin managingmanaging patientpatient care.care. PMPPMP asas anan InvestigativeInvestigative ToolTool

Date filled Patient name Drug name Patient Prescriber address Info. 03/10//2008 “A” APAP/Hydrocod NY, NY Auburndale, one Barbituate FL 03/10/2008 “B” APAP/Hydrocod Cherryhill, NJ Auburndale, one Barbituate FL 03/10/2008 “C” APAP/Hydrocod Edmond, WA Auburndale, one Barbituate FL 03/12/2008 “D” APAP/Hydrocod Walladlade MI Auburndale, one Barbituate FL 03/13/200 “E” APAP/Hydrocod Roanoke, VA Auburndale, one Barbituate FL 03/13/2008 “F” APAP/Hydrocod Hurst, TX Auburndale, one Barbituate FL 03/13/2008 “G” APAP/Hydrocod Pompano Auburndale, one Barbituate Beach, FL FL 21 CFR 1306.04

ToTo bebe effective,effective, aa prescriptionprescription forfor aa controlledcontrolled substancesubstance mustmust bebe issuedissued forfor aa legitimatelegitimate medicalmedical purposepurpose byby anan individualindividual practitionerpractitioner whowho isis actingacting inin thethe usualusual coursecourse ofof hishis professionalprofessional practicepractice MethodsMethods ofof DiversionDiversion

PharmacyPharmacy // OtherOther TheftTheft PractitionersPractitioners // PharmacistsPharmacists ArmedArmed robberyrobbery BurglaryBurglary (Night(Night BreakBreak--ins)ins) IllegalIllegal distributiondistribution InIn--TransitTransit LossLoss (Hijacking)(Hijacking) SelfSelf abuseabuse SmurfingSmurfing TradingTrading drugsdrugs forfor sexsex PatientsPatients EmployeeEmployee pilferagepilferage DrugDrug ringsrings HospitalsHospitals DoctorDoctor--shoppingshopping PractitionersPractitioners’’ officesoffices ForgedForged // fraudulentfraudulent // NursingNursing homeshomes alteredaltered prescriptionsprescriptions RetailRetail pharmaciespharmacies InternetInternet availabilityavailability ManufacturingManufacturing // distributiondistribution facilitiesfacilities InternetInternet DiversionDiversion RogueRogue InternetInternet PharmacyPharmacy ChecksChecks andand BalancesBalances

Physician

Pharmacist Patient OrderingOrdering fromfrom aa RogueRogue SiteSite (Historically)(Historically) buy hydrocodone http://www.drug-prices-and-information.com Order hydrocodone online from our U.S. based licensed pharmacy. No prior prescription needed. No consultation fees. OnlineOnline PharmacyPharmacy ConsultationsConsultations

EasyEasy toto obtainobtain ConvenientConvenient ProblemsProblems withwith OnlineOnline ConsultationsConsultations

AccordingAccording toto AMA,AMA, thisthis methodmethod ofof providingproviding patientspatients withwith prescriptionprescription medicationmedication fallsfalls wellwell belowbelow thethe acceptedaccepted standardstandard ofof medmedicalical carecare FormsForms askask forfor minimalminimal informationinformation NoNo mechanismmechanism toto determinedetermine ifif questionsquestions answeredanswered correctlycorrectly oror truthfullytruthfully NoNo explanationexplanation ofof riskrisk associatedassociated withwith drugdrug NoNo medicalmedical assessmentassessment atat allall NoNo followfollow upup ComponentsComponents necessarynecessary forfor DomesticDomestic RogueRogue InternetInternet OperationOperation

¾ WebWeb BrokerBroker // FacilitatorFacilitator (optional)(optional) ¾ PractitionerPractitioner ¾ PharmacyPharmacy ¾ ****AllAll membersmembers ofof schemescheme areare complicitcomplicit therebythereby eliminatingeliminating allall checkschecks andand balancesbalances ¾ SourceSource ofof SupplySupply C Consumer Dr. Doctor Rx Internet Pharmacy DomesticDomestic WC Web Company 1. Consumer in Montana WS Website Server orders hydrocodone 6. Pharmacy in Iowa S Shipper on the Internet fills order and ships to C Consumer‘‘RR via Shipper WA ’ ME xx’ FlowFlow 4. Order is MTMMT ND MN V approved by T N MA H Physician in OR NY RI New Jersey WI ID SD Rx and returned MI CTT to Web WY PA Company IAIA NJ Dr. NE OH DE NV IL IN UT WV MD CO VA 5. Approved CA KS MO KYY order NC TNS then sent by Web OK SC AZ NM AR Company GA to an MS AL affiliated Pharmacy TX TX LA FL FL WS 2. Request goes WC 3. Web Company through Website (located in Miami, FL) Server in adds request to queue San Antonio, TX for Physician approval HowHow Regulatory/CriminalRegulatory/Criminal EnforcementEnforcement andand LegislationLegislation ChangedChanged thethe LandscapeLandscape CutCut offoff thethe SupplySupply

SeekSeek administrativeadministrative actionaction againstagainst DEADEA registrantsregistrants foundfound toto bebe contributingcontributing toto thethe illegalillegal distributiondistribution ofof controlledcontrolled substancessubstances overover thethe InternetInternet

OrdersOrders ToTo ShowShow CauseCause

ImmediateImmediate SuspensionsSuspensions TheThe DirtyDirty DozenDozen

PHARMACIES CLOSED IN 2007 Total 2006 following Baywatch / Lightning Strike Dosage Units 1. 15,596,380 2. 9,082,010 3. 9,081,976 4. 4,733,290 5. 4,220,840 6. 4,564,480 7. 1,988,600 8. 1,656,450 9. 2,731,420 10. 1,962,620 11. 793,350 12. 1,051,500 TOTAL DOSAGE UNITS 57,462,916 ManufacturersManufacturersManufacturers Flow of Controlled Substances DEA Registrants who are authorized to DEA ReRegistrantsgistrants who are authorized to produce and distribute controlled substances. Rogue Internet Pharmacy pproduceroduce and distribute controlled substances. Typical Internet Diversion (1330 firms including all manufacturers (1(1330330 ffirmsirms includinincludingg all manumanufacturersfacturers Communications and wholesale distributors) Scheme and wholesale distributors)distributors)

Wholesale Distributors ManufacturersManufacturersManufacturers Wholesale Distributors [Re-packagers/Re-labelers] DEA Registrants who are authorized to [Re-packagers/Re-labelers][Re-packagers/Re-labelers] DEADEA RegistrantsRegistrants whowho areare authorizedauthorized toto DEA Registrants who are authorized to distribute controlled substances. DEADEA RegistrantsRegistrants whowho areare authorizedauthorized toto distributedistribute controlledcontrolled substances.substances. package bulk dosage units into consumer-use packagepackage bulkbulk dosagedosage units intointo consumer-useconsumer-usee size packagers and distribute to pharmacies. sizesize packagerspackagers andand distributedistribute toto pharmacies.pharmacies. 2. RIP sends order to practitioner

RogueRogueRogue Internet Internet PharmaciesPharmaciesPharmacies (RIP) (RIP)(RIP) BrickBrick and andand Mortar Mortar Pharmacies Pharmacies Website Operators who Practitioners DEA Registrants who are authorized to WebsiteWebsite OperatorsOperators whowho PractitionersPractitioners DEADEA RegistrantsRegistrants whowho areare authorizedauthorized toto Sell controlled substances DEA Registered doctors, dispense controlled substances to individual customers. SeSellll controlledcontrolled substancessubstancess DEADEA ReRegisteredgistered doctors,doctors, ddispenseispense cocontrolledntrolled subssubstancestances ttoo inindividualdividual customers.customers. over the Internet. nurse practitioners, etc… (64,000 registered pharmacies) ooverver the InteInternet.rnet. nursenurse practitioners,practitioners, etc…etc… ((64,00064,000 reregisteredgistered pharmacies)pharmacies) These entities are who are authorized to TTheseheh se entitiesentities aarere whowho aarere auauthorizedthorized to not registered with issue prescriptions notno rregisteredegistered withwith issueissue prescriptionsprescriptions 3. Practitioner DEA and do not for controlled substances. 4. Pharmacy sends DDEAEA andand do notnot forfor controlledcontrolled substances.substances. sends handle controlled (900,000 Practitioners) controlled hahandlendle controlledcontrolled (900,000(900,000 Practitioners)Practitioners) prescription to substances. Substances subssubstances.tances. pharmacy directly to customer or through RIP

1. Customer places order over CustomersCustomers the Internet ActionsActions TakenTaken

¾ImmediateImmediate SSuspensionsuspensions // OrderOrder toto ShowShow CauseCause ¾ AmerisourceBergenAmerisourceBergen CorpCorp Orlando,Orlando, FLFL ¾ McKessonMcKesson CorpCorp Tampa,Tampa, FLFL

¾ CardinalCardinal CorpCorp $13,250,000$13,250,000 civilcivil penaltypenalty Lakeland,Lakeland, FL;FL; Stafford,Stafford, TX;TX; Swedesboro,Swedesboro, NJ;NJ; andand Auburn,Auburn, WAWA $34,000,000$34,000,000 civilcivil penaltypenalty ¾ BellcoBellco DrugDrug Corp,Corp, LongLong Island,Island, NYNY ¾ Southwood,Southwood, LakeLake Forest,Forest, CACA

¾ VoluntaryVoluntary SurrenderSurrender ¾ RichieRichie Pharmacal,Pharmacal, Glasgow,Glasgow, KYKY CurrentCurrent LegislationLegislation InternetInternet LegislationLegislation SS--980980 H.R.H.R. 63536353 RyanRyan HaightHaight OnlineOnline ConsumerConsumer ProtectionProtection ActAct (signed by the President October 15, 2008) RequiresRequires onlineonline pharmaciespharmacies toto obtainobtain specialspecial DEADEA registrationregistration RequiresRequires identifyingidentifying informationinformation toto bebe postedposted onon thethe webweb sitesite DefinesDefines termsterms suchsuch asas ““onlineonline pharmacypharmacy”” andand ““telemedicinetelemedicine”” ExpandsExpands thethe definitiondefinition ofof aa validvalid prescriptionprescription toto includeinclude atat leastleast oneone inin--personperson medicalmedical evaluationevaluation ofof thethe patientpatient PenaltyPenalty enhancementsenhancements ReportingReporting requirementsrequirements regardingregarding RxRx salessales RyanRyan HaightHaight OnlineOnline PharmacyPharmacy ConsumerConsumer ProtectionProtection ActAct

NewNew DEADEA registrationregistration requirementsrequirements forfor allall InternetInternet pharmaciespharmacies ReportingReporting requirementsrequirements NumberNumber ofof prescriptionsprescriptions DosageDosage unitunit totalstotals

DisclosureDisclosure requirementrequirement onon homehome pagepage Name,Name, address,address, phone,phone, && EE--mailmail ofof allall pharmaciespharmacies NameName && licenselicense ## ofof pharmacistspharmacists inin chargecharge Name,Name, address,address, phone,phone, degreedegree ofof allall physiciansphysicians

StatutoryStatutory implementationimplementation 180180 daysdays fromfrom signingsigning (April 13, 2009) AdaptationAdaptation

¾ FromFrom questionnairesquestionnaires -- toto askingasking forfor medicalmedical recordsrecords ¾FromFrom thethe doctordoctor sendingsending thethe RxRx toto thethe roguerogue pharmacypharmacy -- toto sendingsending itit toto thethe ““patientpatient”” ¾ FromFrom doctorsdoctors locatedlocated inin otherother statesstates -- toto sendingsending ““patientspatients”” toto doctorsdoctors withinwithin thethe samesame statestate ¾SellingSelling nonnon--controlled,controlled, legendlegend drugsdrugs ofof abuseabuse CommonlyCommonly AbusedAbused PrescriptionPrescription ControlledControlled SubstancesSubstances Hydrocodone,Hydrocodone, APAPAPAP C-III

¾ BrandBrand Names:Names: VicodinVicodin®,, LortabLortab®,, LorcetLorcet® ¾ ““CocktailCocktail”” usedused byby drugdrug abusersabusers ¾ Hydrocodone ¾ Soma / carisoprodol ¾ Alprazolam / Xanax® ¾ VicodinVicodin // hydrocodonehydrocodone secondsecond onlyonly toto marijuanamarijuana asas thethe ‘‘drugdrug ofof choicechoice’’ forfor teensteens

¾ *In*In 20042004 U.S.U.S. consumedconsumed 99%99% ofof worldworld’’ss supplysupply ofof hydrocodonehydrocodone yetyet thethe U.S.U.S. makesmakes upup onlyonly 4.5%4.5% ofof thethe worldworld’’ss populationpopulation

*SOURCE: JAMA, January 17, 2007 – Vol 297, No 3, Opioid Prescriptions Soar HydrocodoneHydrocodone GrowthGrowth vs.vs. PopulationPopulation GrowthGrowth 19901990--20072007

¾ BetweenBetween 19901990 andand 20072007

¾ 21%21% growthgrowth inin populationpopulation

¾BetweenBetween 19901990 andand 20072007

¾ **280280%% increaseincrease inin thethe distributiondistribution ofof hydrocodonehydrocodone

*Source: ARCOS (Date Prepared: 04/02/2008) TopTop FiveFive PrescriptionPrescription DrugsDrugs SoldSold inin thethe U.S.U.S. (2005(2005--2007)2007) Note: Percentage change from the number of prescriptions sold in the previous years. 130,000,000 +6.9% (By Number of Prescriptions Sold) +7.9% 110,000,000 +8.5%

90,000,000 117,200,000

70,000,000 109,652,000 101,639,000 50,000,000

30,000,000 61,704,000 62,311,000 52,987,000 55,122,0000 63,219,000 55,039,000 47,829,000 45,777,000 52,104,000 52,803,000 45,124,000 10,000,000 42,747,000 Hydrocodone/APAPLipitor Lisinopril Amoxicillin Hydrochlorothiazide (Pain reliever) (Cholesterol) (Blood pressure) (Antibiotic) (Diuretic) Lipitor Amoxicillin Source: Drug Topics *In 2007 Levothyroxine was #5 Revised September 19, 2008 2005 2006 2007 HydrocodoneHydrocodone Distribution*Distribution* CY2000CY2000--20082008 U.S.U.S. AverageAverage

14,000

12,000 11,870 12,358 10,000 10,749 9,451 8,000 8,670 8,044 6,000 6,777 5,615 4,000 5,083

2,000 Projected

0 GRAMS PER 100K POPULATION 2000 2001 2002 2003 2004 2005 2006 2007 2008

* Includes sales to Retail Registrants, i.e. pharmacies, hospitals, practitioners, teaching institutions, and mid level practitioners

* 01/01/2008-06/30/2008 Source: ARCOS Date Prepared: 09/09/08 NFLISNFLIS NationalNational DataData –– 20062006 && 20072007 NarcoticNarcotic AnalgesicsAnalgesics

Number *Percent Number *Percent

Hydrocodone 26,017 38.85 Hydrocodone 30,504 39.66% %

Oxycodone 19,923 29.75 Oxycodone 24,029 31.24% % Methadone 7,023 10.49 Methadone 7,496 9.75% % Morphine 3,887 5.81% Morphine 4,202 5.46% Codeine 2,597 3.88% Codeine 2,674 3.48% Propoxyphene 1,488 2.22% Propoxyphene 1,306 1.70% Hydromorphon 1,303 1.95% Hydromorphone 1,559 2.03% e Dihydrocodeine 1,290 1.93% Dihydrocodeine 957 1.24% Fentanyl 1,270 1.90% Fentanyl 732 0.95% Buprenorphine 1,113 1.66% Buprenorphine 2,094 2.72%

*Percentage of all narcotic analgesics exhibits analyzed BENZODIAZEPINESBENZODIAZEPINES BenzodiazepinesBenzodiazepines

FirstFirst benzodiazepine,benzodiazepine, chlordiazepoxidechlordiazepoxide waswas approvedapproved forfor useuse inin thethe earlyearly 19601960’’ss

Benzodiazepines,Benzodiazepines, asas aa class,class, areare oneone ofof thethe mostmost widelywidely prescribedprescribed drugsdrugs inin thethe worldworld

TheyThey areare approvedapproved inin thethe U.S.U.S. toto treattreat anxiety,anxiety, insomnia,insomnia, andand seizuresseizures (Sch(Sch IVIV depressantdepressant underunder thethe CSA)CSA)

AdverseAdverse effectseffects include:include: amnesia,amnesia, restlessness,restlessness, delirium,delirium, aggression,aggression, depression,depression, hallucinations,hallucinations, andand paranoiaparanoia NFLISNFLIS NationalNational DataData –– 20062006--20072007 BenzodiazepinesBenzodiazepines 2006 Number Percent 2007 Number Percent of exhibits of exhibits Alprazolam 25,617 62.85% Alprazolam 29,353 65.83%

Clonazepam 6,755 16.56% Clonazepam 7,014 15.73%

Diazepam 6,314 15.48% Diazepam 6,179 13.86%

Lorazepam 1,574 3.86% Lorazepam 1,573 3.53%

Temazepam 326 0.80% Temazepam 295 0.66%

Chlordiazepoxide 100 0.25% Chlordiazepoxide 88 0.20%

Triazolam 50 0.12% Triazolam 57 0.13%

Flunitrazepam 35 0.09% Flunitrazepam 23 0.05%

Midazolam 12 0.03% Midazolam 10 0.02% AlprazolamAlprazolam XanaxXanax®® (Z(Z--bars)bars)

DrugDrug abusersabusers oftenoften preferprefer alprazolamalprazolam duedue toto itsits rapidrapid onsetonset andand longerlonger durationduration ofof actionaction

AlprazolamAlprazolam waswas rankedranked thirdthird inin thethe numbernumber ofof prescriptionsprescriptions forfor controlledcontrolled substancessubstances inin 2003,2003, 2004,2004, 20052005 andand 2006*2006*

ForFor allall salessales ofof genericgeneric pharmaceuticals,pharmaceuticals, alprazolamalprazolam waswas rankedranked 77th****

Source IMS Health ** Source Verispan VONA StatisticalStatistical DataData

FromFrom 20012001 toto 2006,2006, thethe numbernumber ofof seizuresseizures forfor alprazolamalprazolam increasedincreased fromfrom 17,92617,926 toto 29,14329,143 (62%(62% increase)increase)

FromFrom 19951995 toto 2002,2002, EmergencyEmergency DepartmentDepartment visitsvisits involvinginvolving benzodiazepinesbenzodiazepines increasedincreased 41%41% andand fromfrom 20042004 toto 20052005 theythey increasedincreased 19.4%19.4% StateState andand LocalLocal SeizureSeizure DataData

Benzodiazepines Seizures by State/Local

30,000

25,000

Alprazolam 20,000 Chlordiazepoxide Clonazepam Diazepam Flunitazepam 15,000 Lorazepam Midazolam Temazepam Number of Exhibits Number Triazolam 10,000

5,000

0 2000 2001 2002 2003 2004 2005 2006 Year PrescriptionPrescription DataData

Dispensed Presciptions by Year from IMS Health

45,000

40,000

35,000

30,000 ALPRAZOLAM LORAZEPAM 25,000 CLONAZEPAM DIAZEPAM TEMAZEPAM 20,000 CHLORDIAZEPOXIDE TRIAZOLAM MIDAZOLAM

Prescriptions (Thousands) Prescriptions 15,000

10,000

5,000

0 2002 2003 2004 2005 2006 Years OXYCODONE OXYCODONEOXYCODONE PRODUCTSPRODUCTS

OxyContinOxyContin TyloxTylox PercocetPercocet PercodanPercodan NFLISNFLIS NationalNational DataData –– 20062006 && 20072007 NarcoticNarcotic AnalgesicsAnalgesics

Number *Percent Number *Percent

Hydrocodone 26,017 38.85 Hydrocodone 30,504 39.66% %

*Percentage of all narcotic analgesics exhibits analyzed Total prescriptions (expressed in thousands) and average number of dosage units per prescription (shown in parentheses) for oxycodone products. (NPA Plus™, from 2002 thru 2007, data extracted March 2008)

Drug Product 2002 2003 2004 2005 2006 2007 Type

Oxycodone All Products 29,387 32,523 34,790 37,895 42,292 45,878 Combination 19,873 22,022 24,011 26,547 29,366 31,404 oral solid (45.9) (48.5) (50.9) (53) (54.5) (56.6) products Single entity 7,112 7,561 7,294 7,153 7,599 8,078 extended- (69.8) (70.64) (72) (72.77) (73) (73.5) release oral solid products Single entity 2,114 2,642 3,165 3,841 4,948 5,997 immediate- (96) (97.90) (100.3) (100.1) (99.4) (102.6) release oral solid products (exclude liquids) OxycodoneOxycodone Distribution*Distribution* CY2000CY2000--20082008 U.S.U.S. AverageAverage

18,000

16,000 17,002

14,000 15,473

12,000 13,333

10,000 10,50511,107 8,000 9,597 8,056 6,000 7,174

4,000 5,511 Projected

2,000 GRAMS PER 100K POPULATION

2000 2001 2002 2003 2004 2005 2006 2007 2008

* Includes sales to Retail Registrants, i.e. pharmacies, hospitals, practitioners, teaching institutions, and mid level practitioners

Source: ARCOS Date Prepared: 09/09/08 NFLIS Cases by Drug

30,000

25,000

20,000

2002 2003 15,000 2004 2005 2006 Number of Cases of Number 10,000 2007 2008*

5,000

0 Tramadol Hydromorphone Carisoprodol Oxycodone Alprazolam Hydrocodone Drugs *January- September 2008 METHADONEMETHADONE

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INDICATIONS

PainPain TreatmentTreatment

NarcoticNarcotic AddictionAddiction Treatment/MaintenanceTreatment/Maintenance DosageDosage FormsForms

TabletsTablets 55 mg/mg/ 1010 mgmg DiskettesDiskettes 4040 mgmg LiquidLiquid MethadoneMethadone -- PharmacologyPharmacology

MethadoneMethadone belongsbelongs toto pharmacologicalpharmacological classclass calledcalled ““OpioidsOpioids””

OpioidsOpioids (e.g.,(e.g., hydrocodone,hydrocodone, oxycodone,oxycodone, morphine,morphine, hydromorphone,hydromorphone, fentanyl)fentanyl) areare amongamong thethe mostmost potentpotent analgesicanalgesic drugsdrugs andand areare widelywidely usedused

OpioidsOpioids areare usedused inin thethe managementmanagement ofof acuteacute andand cancercancer--relatedrelated pain,pain, andand chronicchronic nonnon--cancercancer painpain

OpioidOpioid analgesicsanalgesics affectaffect numbernumber ofof systemssystems –– CNS,CNS, cardiovascular,cardiovascular, GIGI tract,tract, ImmunologicalImmunological etc.etc. MethadoneMethadone –– AnalgesiaAnalgesia

ActionsActions onon CNSCNS –– RelievesRelieves painpain EquivalentEquivalent toto morphinemorphine inin effectivenesseffectiveness ItsIts eliminationelimination isis slowerslower thanthan itsits durationduration (4(4--88 hours)hours) ofof actionaction PatientPatient maymay feelfeel thethe needneed toto repeatrepeat dosedose atat intervalsintervals shortershorter thanthan bodybody cancan handlehandle RepeatedRepeated dosingdosing leadsleads toto accumulationaccumulation inin thethe bodybody thatthat maymay causecause seriousserious toxicitytoxicity MethadoneMethadone UseUse inin PainPain ManagementManagement 55 andand 1010 mgmg methadonemethadone tabletstablets -- approvedapproved forfor useuse inin painpain managementmanagement 4040 mgmg diskettesdiskettes –– notnot approvedapproved forfor analgesicanalgesic useuse FDAFDA alertalert –– PhysiciansPhysicians shouldshould avoidavoid prescribingprescribing 4040 mgmg diskettediskette forfor painpain ARCOSARCOS datadata indicatesindicates thatthat 4040 mgmg diskettesdiskettes areare beingbeing increasinglyincreasingly prescribedprescribed forfor painpain managementmanagement ThisThis isis aa causecause forfor concernconcern becausebecause aa 4040 toto 5050 mgmg methadonemethadone cancan bebe lethallethal inin opioidopioid--naïvenaïve individualindividual MethadoneMethadone -- ToxicityToxicity

Respiratory depression Major hazard (Similar to other opioid analgesics) Respiratory depression typically occurs later and persist longer than its peak analgesic effects Drug Interactions CNS depressants (Alcohol, other opioids or CNS depressants) CYP3A4 inhibitors (some antifungal agents, macrolide antibiotics, and SSRIs) MethadoneMethadone DeathsDeaths–– TwoTwo MajorMajor MechanismsMechanisms

ToxicityToxicity onon heartheart QTQT IntervalInterval prolongationprolongation andand TorsadesTorsades dede PointesPointes (TdP)(TdP) –– SharedShared byby LAAMLAAM,, butbut notnot byby otherother opioidsopioids MayMay leadlead toto ventricularventricular fibrillationfibrillation andand deathdeath MethadoneMethadone SingleSingle DoseDose KineticsKinetics

INTOXICATON

T½ 5-6 ANALGESIA hrs

PAIN T½ 20-40 hrs

Pain” 5101520 Time (hrs)

Ref: Nilsson MI, et al. Acta anaesth. scand 1982, Suppl 74, 66-69 Source: Resource Manual for CME course entitled “Prescribing Opioids for Chronic – Offered by the New England Chapters of the American Society of Addiction Medicine with support form CSAT, SAMHSA FixedFixed MethadoneMethadone DoseDose IntervalInterval

TOXICITY

ANALGESIA

PAIN Pain”

Dosage intervals Ref: Nilsson MI, et al. Acta anaesth. scand 1982, Suppl 74, 66-69 Source: Resource Manual for CME course entitled “Prescribing Opioids for Chronic – Offered by the New England Chapters of the American Society of Addiction Medicine with support form CSAT, SAMHSA MethadoneMethadone MortalityMortality AssessmentsAssessments byby SAMHSASAMHSA-- FindingsFindings

SAMHSA convened two meetings (2003 and 2007) to assess the factors behind increase in methadone related deaths Accumulation to toxic levels of methadone during the start of opioid treatment or pain management due to overestimation of tolerance and methadone’s long, often variable, half-life. Misuse of diverted methadone by individuals with little or no opioid tolerance. Synergistic effects of methadone combined with other CNS depressants (i.e., alcohol, benzodiazepines or other opioids). Increasing use of methadone in pain management may be an important contributing factor WhoWho isis PrescribingPrescribing Methadone?Methadone?

55 andand 1010 mgmg tabletstablets 4040 mgmg diskettesdiskettes RxRx RxRx TopTop Prescribers:Prescribers: TopTop Prescribers:Prescribers: •• FamilyFamily PractitionersPractitioners • AnesthesiologistsAnesthesiologists •• AnesthesiologistsAnesthesiologists • FamilyFamily PractitionersPractitioners •• InternistsInternists • InternistsInternists •• OsteopathsOsteopaths • OsteopathsOsteopaths •• PhysicalPhysical Med.Med. && RehabRehab • PhysicalPhysical Med.Med. && •• NurseNurse PractitionersPractitioners Rehab Rehab •• GeneralGeneral PractitionersPractitioners • • NeurologistsNeurologists Source: IMS Health, National Prescription Audit, November 2006 • NurseNurse PractitionersPractitioners METHADONEMETHADONE POISONING/DEATHPOISONING/DEATH DATADATA NFLISNFLIS NationalNational DataData –– 20062006 && 20072007 NarcoticNarcotic AnalgesicsAnalgesics

Number *Percent Number *Percent

Hydrocodone 26,017 38.85 Hydrocodone 30,504 39.66% %

*Percentage of all narcotic analgesics exhibits analyzed %% IncreaseIncrease inin PoisoningPoisoning DeathsDeaths inin thethe U.S.U.S. SinceSince 19991999 Source: CDC

500 All poisoning 400 deaths e Methadone 300 Other opioid 200

100 Other synthetic narcotics % Increas % 0 Cocaine

-100 2000 2001 2002 2003 2004 2005 TotalTotal PrescriptionsPrescriptions –– SelectedSelected OpioidOpioid analgesicsanalgesics Source: IMS Health 140 Prescription Audit Plus

120 (NPA Plus™) 100 ™ 80 hydrocodone 60 oxycodone 40 methadone 20 0 Prescriptions (millions) Prescriptions Prescriptions (millions) Prescriptions 2003 2004 2005 2006 2007 Note: In 2006, there were about 33-fold more hydrocodone prescriptions,11-fold more oxycodone prescriptions compared to methadone prescriptions Deaths/100,000Deaths/100,000 PrescriptionsPrescriptions inin FloridaFlorida

Source: FDLE and NPA Plus™

2006 2007

400

300

200

100 Prescriptions Prescriptions Deaths/100,000 Deaths/100,000 0 Hyr Oxy Metha doc codone done odone MethadoneMethadone DistributionDistribution DataData MethadoneMethadone DistributionDistribution byby BusinessBusiness ActivityActivity Source: DEA ARCOS

5,000

4,000

3,000

2,000

1,000

0 2000 2001 2002 2003 2004 2005 2006

NTP's Pharmacies Hospitals Practitioners GRAMS PER 100K POPULATION GRAMS PER GRAMS PER 100K POPULATION GRAMS PER

1,574

3,041

4, 8

Source: DEA ARCOS 4,31

Excludes NTP’s 4,812

OR WA NV ME AL U.S.

1,589

3,043

120

3, 2

342 4,

TOP 5 STATES (2006) TOP 5 STATES (2006) 4,817 Includes NTP’s - - OR WA NV ME AL U.S. 0

5,000 4,000 3,000 2,000 1,000

Distribution of 5 and 10 mg Tablets Distribution of 5 and 10 mg Tablets GRAMS PER 100K POPULATION 100K PER GRAMS Purchases*Purchases* ofof 4040 mgmg DiskettesDiskettes byby BusinessBusiness ActivityActivity -- 20062006

Source: DEA ARCOS 810 Hospitals Source: DEA ARCOS 19,27519,275 45,329 grams (1.40%) PharmaciesPharmacies 1,676,2251,676,225 gramsgrams 5858 PractitionersPractitioners 44,28544,285 gramsgrams (1.37%)(1.37%) 51.851.8 %% 45.445.4 %% First Half 2007 (01/01/07- 06/30/07) 424424 NTP’sNTP’s 56.3%56.3% 1,470,5661,470,566 gramsgrams 41.2%41.2% ** BasedBased onon totaltotal gramgram amountamount MethadoneMethadone HydrochlorideHydrochloride 4040 mgmg AdvisoryAdvisory

AsAs ofof JanuaryJanuary 1,1, 2008,2008, manufacturersmanufacturers ofof methadonemethadone hydrochloridehydrochloride tabletstablets 4040 mgmg (dispersible)(dispersible) havehave voluntarilyvoluntarily agreedagreed toto restrictrestrict distribution.distribution.

TheThe 5mg5mg andand 1010 mgmg formulationsformulations indicatedindicated forfor thethe treatmenttreatment ofof painpain willwill continuecontinue toto bebe availableavailable toto allall authorizedauthorized registrants,registrants, includingincluding retailretail pharmacies.pharmacies. OtherOther ControlledControlled SubstancesSubstances StimulantsStimulants

PhenterminePhentermine PhendimetrazinePhendimetrazine MethylphenidateMethylphenidate (CII)(CII) AmphetamineAmphetamine ALKSALKS (CII)(CII) Non-Controlled Substances

Analgesic:Analgesic: TramadolTramadol (Ultram(Ultram®®,, UltracetUltracet®®)) ControlledControlled SubstanceSubstance inin OK,OK, AR,AR, KYKY MuscleMuscle Relaxant:Relaxant: CarisoprodolCarisoprodol (Soma(Soma®®)) ControlledControlled inin 1818 StatesStates Carisoprodol OO H N O O NH H 2 CH3 Structural Change H3C by Enzymatic Action in the Body

OO (H C)(H C)HC 3 3 N O O NH2 H CH3 H C 3 Meprobamate AnabolicAnabolic Steroids,Steroids, DietaryDietary SupplementsSupplements andand hGHhGH Steroid Use is all about appearance, not performance WHY????WHY????

ToTo GainGain anan EdgeEdge onon thethe CompetitionCompetition…….. AnabolicAnabolic SteroidsSteroids inin thethe USAUSA

Schedule III of the Controlled Substances Act

59 Steroids under control in U.S. AnabolicAnabolic SteroidsSteroids

“Performance“ enhancing” drugs

Synthetic testosterone

Available as injectables, tablets, capsules, gels, and creams AnabolicAnabolic SteroidsSteroids

Build tissue up (“anabolic”) by increasing protein synthesis and nitrogen retention (e.g., stimulate healing in burn victims). Treat some forms of anemia. Synthetic variations on the testosterone molecule, these are “androgens” and thus have masculinizing effects (“androgenic”) as well as anabolic. More properly called “anabolic-androgenic steroids” (or AAS). ChemistryChemistry && PharmacologyPharmacology

PromotePromote growthgrowth ofof skeletalskeletal andand cardiaccardiac muscle;muscle; IncreaseIncrease bonebone density;density; IncreaseIncrease redred bloodblood cellscells IndicatedIndicated forfor treatingtreating specificspecific typestypes ofof anemia,anemia, somesome breastbreast cancers,cancers, osteoporosis,osteoporosis, endometriosisendometriosis EndocrineEndocrine dysfunction/hypogonadidysfunction/hypogonadi sm/growthsm/growth retardationretardation IllicitIllicit UseUse

OnlyOnly aa smallsmall numbernumber ofof anabolicanabolic steroidssteroids areare approvedapproved forfor humanhuman oror veterinaryveterinary useuse IllicitIllicit steroidssteroids areare soldsold atat gyms,gyms, competitionscompetitions andand throughthrough mailmail order/Internetorder/Internet operationsoperations SteroidsSteroids areare alsoalso diverteddiverted fromfrom pharmacies,pharmacies, physiciansphysicians oror synthesizedsynthesized inin clandestineclandestine laboratorieslaboratories Synthesis of Testosterone InjectableInjectable SteroidsSteroids

Absorbed directly into the blood stream, avoiding a first pass through the liver. Intramuscular, not intravenous. Most injectable steroids undergo a process called esterification to slow their release into circulation. One Cycle – Approximately 12 Weeks

Esquire Magazine, April 2008 – “Look at Me! I’m a Big Strong Boy” by Craig Davidson

35 Pound Increase in Body Weight

Single Workout Bench Press Increase of 30 Pounds

Esquire Magazine, April 2008 – “Look at Me! I’m a Big Strong Boy” by Craig Davidson

Side Effects of Steroid Use: Women

SteroidSteroid AbuseAbuse

DECA SUSTANON DURABOLIN DIANABOL Tabs.

CommonCommon SteroidsSteroids AbusedAbused CommonlyCommonly AbusedAbused SteroidsSteroids

InjectableInjectable SteroidsSteroids OralOral SteroidsSteroids ƔƔ DecaDeca--DurabolinDurabolin ƔƔ AnadrolAnadrol (nandrolone(nandrolone decanoate)decanoate) (oxymetholone)(oxymetholone) ƔƔ DurabolinDurabolin ƔƔ OxandrinOxandrin (nandrolone(nandrolone phenproionate)phenproionate) (oxandrolone)(oxandrolone) ƔƔ DepoDepo--TestosteroneTestosterone ƔƔ DianabolDianabol (testosterone(testosterone cypionate)cypionate) (methandrostenolone)(methandrostenolone) ƔƔ EquipoiseEquipoise ƔƔ WinstrolWinstrol (boldenone(boldenone undecylenate)undecylenate) (stanozolol)(stanozolol) ƔƔ TetrahydrogestrinoneTetrahydrogestrinone (THG)(THG) PatternsPatterns ofof SteroidSteroid AbuseAbuse

Cycling:: alternatingalternating periodsperiods ofof anabolicanabolic steroidsteroid useuse (on(on cycle)cycle) withwith periodsperiods ofof eithereither nono useuse oror thethe useuse ofof lowlow dosesdoses ofof anabolicanabolic steroids.steroids.

StackingStacking:: concurrentconcurrent useuse ofof twotwo oror moremore steroidssteroids together.together.

StackingStacking thethe PyramidPyramid oror PyramidingPyramiding:: increaseincrease inin thethe dose/typedose/type earlyearly inin thethe cyclecycle andand taperingtapering thethe dosedose inin thethe latterlatter partpart ofof thethe cycle.cycle. SteroidSteroid AbuseAbuse

STRIDE Data

Oxandrolone

stanazolol

testosterone 0 100 200 300

Number of Federal Cases

Number of Federal Cases Involving the most frequently encountered steroids. 2007 STRIDE Data. TRAFFICKINGTRAFFICKING TRENDSTRENDS

Source Areas/Countries: Mexico, Eastern Europe, China (Precursors), and Australia.

Mexico was the most significant manufacturer of steroids seized in the United States.

U.S. customers were purchasing from Mexican pharmacies.

Purchasers then smuggle back across border, or mail from Mexico.

“Operation Gear Grinder” targeted 8 Mexican veterinary steroid manufacturers whose products were illegally via the Internet. TRENDSTRENDS (Cont.)(Cont.)

Shift to bulk purchase- Illegal clandestine steroid manufacturing laboratories have become more abundant than they have in the past.

Operation Raw Deal

Online auction sites (e.g. eBay, Yahoo and similar sites) are cooperating with law enforcement, but distributors have altered the methods of describing their products to avoid the filters these companies use to find illegal/illicit products.

Internet sales from foreign-based web sites to include Prohormones and Steroid precursors

Prescription Mills OperationOperation RawRaw DealDeal

11.4 million steroid dosage units were seized OperationOperation RawRaw DealDeal

Raw material obtained from China and other countries Internet message boards and chat rooms provided info on how to convert raw material Promote and sell conversion kits OperationOperation RawRaw DealDeal

Two-year international investigation

U.S., Mexico, Canada, China, Belgium, Australia, Germany, Denmark, Sweden, and Thailand

Anabolic steroids, HGH, insulin growth factor

124 arrests, and 56 U.S. steroid labs seized COUNTERFEITSCOUNTERFEITS OROR ““BUNKBUNK”” STEROIDSSTEROIDS

SignificantSignificant quantitiesquantities ofof counterfeitcounterfeit steroidssteroids availableavailable onon thethe blackblack market.market. BasedBased onon seizureseizure statistics,statistics, thisthis numbernumber couldcould bebe 15%15% oror higher.higher.

SomeSome ofof thethe injectableinjectable bunkbunk steroidssteroids analyzedanalyzed havehave containedcontained oliveolive oiloil andand sesamesesame oil.oil. HumanHuman GrowthGrowth HormoneHormone (hGH)(hGH)

AlsoAlso knownknown asas somatotropinsomatotropin ItIt isis synthesizedsynthesized andand secretedsecreted byby cellscells ofof thethe anterioranterior pituitary.pituitary. Gigantism,Gigantism, acromegaly,acromegaly, hypothyroidism,hypothyroidism, cardiaccardiac disease,disease, myopathies,myopathies, arthritis,arthritis, diabetes,diabetes, impotence,impotence, osteoporosis.osteoporosis. MostMost IllicitIllicit hGHhGH obtainedobtained fromfrom foreignforeign sources/Internetsources/Internet--JintropinJintropin Injection***Injection*** hGHhGH

ConsideredConsidered aa PartitioningPartitioning AgentAgent NotNot AnabolicAnabolic RegulatesRegulates bodybody composition,composition, glucoseglucose andand lipidlipid metabolism,metabolism, skeletalskeletal musclemuscle andand bonebone growth.growth. HumanHuman GrowthGrowth HormoneHormone

The 1990 law inserted growth hormone into 21 U.S.C. § 333, the Steroid Trafficking Act.

Indicated in adults for Aids Wasting, Short Bowel Syndrome and hGH deficiency (1 in 10,000).

Technically, notnot a controlled substance (federal). But, … federal law criminalizes whoever knowingly distributes, or possesses with intent to distribute, human growth hormone for any use in humansrecognizedrecognizedotherother medicalmedical thanthan the the conditioncondition treatmenttreatment ofof aa diseasedisease oror otherother . 21 USC 333(e)

DEA has authority to investigate. HumanHuman GrowthGrowth HormoneHormone U.S.U.S. ProductsProducts

Genotropin Humatrope Norditropin Nutropin Saizen GrowthGrowth HormoneHormone ReleasersReleasers

AlsoAlso calledcalled ““hGHhGH Releasers,Releasers,”” ““hGHhGH Precursors,Precursors,”” ““hGHhGH SecretagoguesSecretagogues”” TheyThey dodo notnot containcontain hGH,hGH, theythey willwill readread ““hGHrhGHr”” –– aa compilationcompilation ofof aminoamino acids.acids. DietaryDietary SupplementsSupplements DRUGSDRUGS SUPPLEMENTSSUPPLEMENTS

MustMust bebe provenproven MustMust bebe provenproven safesafe beforebefore harmfulharmful beforebefore approvedapprovedforfor removedremovedfromfrom marketmarket marketmarket DietaryDietary SupplementsSupplements

DefinitionDefinition ofof productsproducts thatthat cancan bebe soldsold asas dietarydietary supplements:supplements:

ŹŹAA productproduct (other(other thanthan tobacco)tobacco) intendedintended toto supplementsupplement thethe diet.diet. TheThe productproduct containscontains oneone oror moremore ofof thethe following:following: vitamin;vitamin; mineral;mineral; herbherb oror otherother botanic;botanic; aminoamino acid;acid; dietarydietary substancesubstance forfor useuse byby humans;humans; oror aa concentrate,concentrate, metabolite,metabolite, constituent,constituent, extractextract oror combinationcombination ofof thesethese ingredients.ingredients.

ŹŹTheThe productproduct mustmust alsoalso bebe intendedintended forfor ingestioningestion andand cannotcannot bebe advertisedadvertised forfor useuse asas aa food.food. DesignerDesigner SteroidsSteroids AnabolicAnabolic SteroidSteroid ControlControl ActAct ofof 20042004

OnOn AprilApril 25,25, 2008,2008, DEADEA PublishedPublished aa NoticeNotice ofof ProposedProposed RulemakingRulemaking toto placeplace inin ScheduleSchedule IIIIII thethe followingfollowing substances:substances: ¾ AndrostaAndrosta--1,41,4--dienediene--3,173,17--dionedione (Boldione)(Boldione) ¾ DesoxymethyltestosteroneDesoxymethyltestosterone ¾ 1919--nornor--4,9(10)4,9(10)--androstadienedioneandrostadienedione TheseThese drugsdrugs areare chemicallychemically andand pharmacologicallypharmacologically similarsimilar toto testosterone;testosterone; areare notnot progestins,progestins, estrogensestrogens oror corticosteroidscorticosteroids andand areare notnot DHEADHEA Salvia Divinorum And Salvinorin A SalviaSalvia DivinorumDivinorum

RelatedRelated toto thethe mintmint familyfamily ((LabiataeLabiatae oror LamiaceaeLamiaceae).). HundredsHundreds ofof species.species. PerennialPerennial herb.herb. IndigenousIndigenous toto thethe StateState ofof OaxacaOaxaca inin Mexico.Mexico. OneOne ofof severalseveral "vision"vision--inducing"inducing" plantsplants employedemployed byby thethe MazatecMazatec IndiansIndians livingliving inin thethe mountainsmountains andand uplandsuplands valleysvalleys ofof northeasternnortheastern OaxacaOaxaca inin Mexico.Mexico. Other Names

• Salvia • Mexican Mint • Magic Mint • Diviner's Sage • Ska Pastora • Ska Maria Pastora • Sage of the Seers • Leaves of the Shepherdess CharacteristicCharacteristic FeaturesFeatures ofof SalviaSalvia DivinorumDivinorum PlantPlant

GrowsGrows toto wellwell overover oneone metermeter inin height.height. HasHas largelarge (6(6 inches)inches) ovateovate greengreen leavesleaves finelyfinely dentateddentated alongalong thethe margin.margin. HasHas hollowhollow squaresquare stems.stems. HasHas blossomsblossoms withwith whitewhite corollascorollas andand purplepurple calyces.calyces. Salvia Divinorum As Sold Over the Internet

Internet sites advertise Salvia as a legal alternative to other controlled hallucinogens. Sold as: • Seeds • Fresh Leaves • Dried Leaves • Whole Plants • Cuttings • Extracts (5x,10x,15x,20x) Exhibits of Salvia Found to Contain Salvinorin A

Salvia from Rochester, Minnesota. Salvia from Dade County, Florida

Images were obtained from Microgram Salvia Divinorum Use in the U.S.

Quid method - chewing fresh leave and retaining the leaf mass and juice in the cheek (like chewing tobacco). Smoking of dried leaves. (Preferred mode of administration by users in the U.S.) There are anecdotal reports of abuse, but no data from standard drug abuse databases (e.g., DAWN and Poison Control) within the U.S. to accurately estimate the extent of abuse EffectsEffects

PsychoactivePsychoactive effectseffects (when(when theythey occur)occur) startstart inin aboutabout 1515 toto 3030 secondsseconds afterafter smoking,smoking, 44--1010 minutesminutes afterafter chewingchewing andand holdingholding inin cheekcheek ofof mouthmouth andand 2020--3030 minutesminutes afterafter oraloral ingestion.ingestion. TheseThese effectseffects maymay include:include: -- VisualVisual hallucinationshallucinations withwith brightbright lights,lights, vividvivid colorscolors withwith distortiondistortion ofof realreal imagesimages andand seeingseeing imagesimages thatthat areare notnot there.there. -- OutOut ofof bodybody experienceexperience likelike thatthat ofof ketamineketamine (CIII).(CIII). PhysicalPhysical EffectsEffects includeinclude lacklack ofof coordination,coordination, dizzinessdizziness andand slurredslurred speech.speech. SalvinorinSalvinorin AA O H O O O H H SubstanceSubstance thoughtthought toto bebe responsibleresponsible H 3 CCO O forfor thethe psychoactivepsychoactive effectseffects ofof salvia.salvia. CH3 CH3 H COC HasHas aa uniqueunique chemicalchemical structurestructure unlikeunlike 3 O otherother hallucinogens.hallucinogens. OnlyOnly recentlyrecently havehave analyticalanalytical techniquestechniques beenbeen developeddeveloped toto evaluateevaluate thisthis chemicalchemical inin humans.humans. PresentPresent inin drydry leavesleaves atat concentrationsconcentrations ofof aboutabout 11--44 mgmg perper gramgram ofof drydry leafleaf InIn humanhuman studiesstudies -- Smoking of dried leaves or up to 2.6 mg Salvinorin A, produced psychoactive effects in about 30 seconds, peaking at about 10 minutes and lasting 15-30 minutes SalvinorinSalvinorin AA HowHow maymay itit exertexert psychoactivepsychoactive effects?effects?

DoesDoes notnot bindbind atat receptorsreceptors normallynormally associatedassociated withwith thethe psychoactivepsychoactive effectseffects ofof currentlycurrently controlledcontrolled substancessubstances includingincluding dopamine,dopamine, serotonin,serotonin, benzodiazepine,benzodiazepine, oror cannabinoidcannabinoid receptors.receptors.

DoesDoes bindbind withwith highhigh affinityaffinity toto opioidopioid kappakappa receptors.receptors.

KappaKappa receptorreceptor activationactivation isis knownknown toto bebe associatedassociated withwith hallucinationshallucinations andand otherother dysphoricdysphoric (unpleasant)(unpleasant) effects.effects. RegulatoryRegulatory ControlsControls

SalvinorinSalvinorin AA isis notnot currentlycurrently controlledcontrolled underunder thethe ControlledControlled SubstancesSubstances ActAct inin thethe UnitedUnited States.States.

BillBill inin 20022002 -- "Hallucinogen"Hallucinogen ControlControl ActAct ofof 2002"2002" -- ProposedProposed toto placeplace SalvinorinSalvinorin AA andand SalviaSalvia DivinorumDivinorum intointo ScheduleSchedule I.I. ItIt waswas notnot reintroducedreintroduced inin 2003.2003.

AA numbernumber ofof U.S.U.S. statesstates havehave takentaken legallegal actionaction

SalvinorinSalvinorin DivinorumDivinorum isis controlledcontrolled inin Finland,Finland, Denmark,Denmark, AustraliaAustralia andand Italy.Italy. InIn NorwayNorway itit isis notnot controlledcontrolled butbut listedlisted asas aa psychoactivepsychoactive drug.drug. DDEEAA WWeebb ssiitteess

ForFor AdditionalAdditional InformationInformation

www.DEAdiversion.usdoj.gov or www.dea.gov ThankThank You!You!