phencyclidine: dust, dippers, & death - welcome to the

Phencyclidine: Phencyclidine: Dust, Dippers, & DeathDust, Dippers, & Death

Eucen FuEucen FuLos Angeles County Los Angeles County

Department of CoronerDepartment of Coroner18 June 200418 June 2004

CAT Summer 2004CAT Summer 2004

ObjectivesObjectives

Basic Understanding of PCPBasic Understanding of PCPOur Method of AnalysisOur Method of AnalysisOur ResultsOur ResultsInteresting CasesInteresting Cases

HistoryHistory

First Synthesized in 1926First Synthesized in 1926Properties not investigated until 1956 by Properties not investigated until 1956 by ParkeParke--DavisDavisAnimals exhibited anesthetic properties Animals exhibited anesthetic properties Therapeutic index for humans was 5x Therapeutic index for humans was 5x greater than existing anestheticsgreater than existing anesthetics

HistoryHistory

Approved for use Approved for use -- 1960 U.K, 1963 U.S.1960 U.K, 1963 U.S.England Patent 836,083England Patent 836,083U.S. Patent 3,097,136U.S. Patent 3,097,136SerynlSerynl –– anesthetic in humansanesthetic in humansPost Surgery Post Surgery –– Adverse ReactionsAdverse Reactions

HistoryHistory1963 1963 –– Discontinued for human useDiscontinued for human useSernylanSernylan used as large animal veterinarian used as large animal veterinarian tranquilizer until 1979tranquilizer until 1979Popular street drug “Peace Pill” in S.F. in Popular street drug “Peace Pill” in S.F. in 1967+1967+PCP last legally manufactured in the U.S. PCP last legally manufactured in the U.S. 19791979Canada still uses PCP as an animal Canada still uses PCP as an animal tranquilizer?tranquilizer?

P CP C PP11--(1(1--phenylcyclohexylphenylcyclohexyl))--piperidinepiperidine

MW: 243.38MW: 243.38

CC1717HH2525NN

pKa pKa = 8.5= 8.5

Schedule IISchedule II

PCP vs. KetaminePCP vs. Ketamine

Ketamine similar to PCP Ketamine similar to PCP Dissociative AnestheticDissociative AnestheticHuman and Animal AnestheticHuman and Animal AnestheticSchedule IIISchedule III

CC1313HH1616ClNOClNO

CC1717HH2525NN

11--(1(1--phenylcyclohexylphenylcyclohexyl))--piperidinepiperidine

TT1/21/2 = 7= 7--46 hours (21 hrs)46 hours (21 hrs)Vd Vd = 5.3= 5.3--7.5 L/Kg7.5 L/KgLipophilicLipophilicDissociative AnestheticDissociative AnestheticNot classified as HallucinogenNot classified as Hallucinogen

NicknamesNicknamesAngel dustAngel dust DipsDipsElephantElephant HogHogEmbalming Fluid Embalming Fluid FormaldehydeFormaldehydeOzoneOzone Rocket fuelRocket fuelSuper Super koolskools TicTacTicTacTranqTranq WetWetSernylanSernylan SernylSernylAnimal TranquilizerAnimal Tranquilizer THCTHC

What does it look like?What does it look like?Bitter, Oily LiquidBitter, Oily Liquid

White Crystalline PowderWhite Crystalline Powder

How synthesized?How synthesized?Reagents include:Reagents include:Piperidine, Piperidine, CyclohexanoneCyclohexanone, Water, , Water, Sodium Meta Bisulfite, Bromo Benzene, Sodium Meta Bisulfite, Bromo Benzene, Magnesium Turnings, HCl, Magnesium Turnings, HCl, Sodium Cyanide, EtherSodium Cyanide, Ether

Grignard Reaction in a well ventilated Grignard Reaction in a well ventilated areaarea

TidbitsTidbits

PCC precursor most likely to show up in PCC precursor most likely to show up in final product unless another cleanup final product unless another cleanup stepstepUsually salt form if solidUsually salt form if solid

Mostly sold as Mostly sold as liquidliquid

Routes of AdministrationRoutes of Administration

Primarily Smoking (1Primarily Smoking (1--3 mg)3 mg)

Insufflation (1Insufflation (1--3 mg)3 mg)

Ingestion (2Ingestion (2--6 mg)6 mg)

IV (1IV (1--3 mg)3 mg)

Routes of AdministrationRoutes of Administration

Initially IV when used as anestheticInitially IV when used as anestheticThen orally as “Peace Pill”Then orally as “Peace Pill”Nowadays it’s mostly smoked:Nowadays it’s mostly smoked:

PCP Crystals sprinkled on MJPCP Crystals sprinkled on MJMJ Cigarettes dipped in PCPMJ Cigarettes dipped in PCPLiquid PCP sprinkled over parsley/mint Liquid PCP sprinkled over parsley/mint and then rolledand then rolled

DosageDosage

OralOralBioavailability 50Bioavailability 50--90%90%1 mg 2.71 mg 2.7--2.9 ng/ml2.9 ng/ml 1.5 hr1.5 hr

SmokingSmokingEffects w/in first few minutesEffects w/in first few minutes40% of PCP Inhaled, 30% as PC40% of PCP Inhaled, 30% as PCPeak plasma [ ] 5Peak plasma [ ] 5--2020 minsmins

Dosage and EffectsDosage and EffectsAvg. high lasts 4Avg. high lasts 4--6 hours6 hoursCome down 6Come down 6--24 hours24 hours

11--5 mg5 mg Euphoria/numbness (alcohol)Euphoria/numbness (alcohol)55--10 mg10 mg Excited/confused, repetitive motor Excited/confused, repetitive motor

movements, fevermovements, fever>20 mg>20 mg Coma/death, respiratory depressionComa/death, respiratory depression

Mechanism of ActionMechanism of ActionPCP effects a number of neurotransmitter PCP effects a number of neurotransmitter systems:systems:

dopaminergic agonist effectsdopaminergic agonist effectsnicotinic and muscarinic cholinergic systemsnicotinic and muscarinic cholinergic systemsNN--methylmethyl--DD--aspartate (NMDA) antagonist aspartate (NMDA) antagonist effectseffectsand noradrenergic and serotonergic and noradrenergic and serotonergic neurotransmissionneurotransmission

It exhibits stimulant, depressant, It exhibits stimulant, depressant, hallucinogenic, and analgesic propertieshallucinogenic, and analgesic properties

PharmacodynamicsPharmacodynamics

Rappolt Rappolt et al. came up with 3 categorieset al. came up with 3 categoriesI: Mild impairment/confusion I: Mild impairment/confusion

II: Deeper psychiatric disturbances and II: Deeper psychiatric disturbances and spasmsspasms

III:ComaIII:Coma

PharmacodynamicsPharmacodynamics

StageStage PCP Level ng/mlPCP Level ng/ml TimeTimeII <100 <100 44--8 hrs8 hrs

IIII 100100--300 300 Several HoursSeveral Hours

1212--24 hrs24 hrsIIIIII >300>300 10 days10 days

PharmacokineticsPharmacokinetics

No controlled pharmacokinetic studies No controlled pharmacokinetic studies using psychoactive doses have been using psychoactive doses have been performed. But abuse has permitted performed. But abuse has permitted estimation.estimation.

There does not appear a direct There does not appear a direct correlation between blood PCP correlation between blood PCP concentration and behavior.concentration and behavior.

PharmacokineticsPharmacokinetics

Liver metabolism Liver metabolism –– oxidative hydroxylationoxidative hydroxylation2 inactive metabolites2 inactive metabolitesAvg. 77% of IV dose found in urine/feces Avg. 77% of IV dose found in urine/feces after 10 daysafter 10 daysRenal clearance of PCP depends heavily on Renal clearance of PCP depends heavily on urine pHurine pH

DRE Physical ObservationsDRE Physical ObservationsHorizontal gaze nystagmusHorizontal gaze nystagmusVertical gaze nystagmus Vertical gaze nystagmus Lack of convergence presentLack of convergence presentPupil size normal Pupil size normal Reaction to light normalReaction to light normalPulse rate elevatedPulse rate elevatedBlood pressure elevatedBlood pressure elevatedBody temperature elevatedBody temperature elevated

DRE Physical ObservationsDRE Physical Observations

Rigid musclesRigid musclesCyclic behaviorCyclic behaviorSudden turn to violenceSudden turn to violenceLack of response to painful stimuliLack of response to painful stimuliBlank stareBlank stareSweatingSweatingIncomplete or delayed verbal responsesIncomplete or delayed verbal responses

Tolerance, Dependence and Tolerance, Dependence and Withdrawal Effects:Withdrawal Effects:

Tolerance may develop. Tolerance may develop. Possibly psychological addicting. Possibly psychological addicting. No physical dependency in humans. No physical dependency in humans. Upon abrupt discontinuation, physical Upon abrupt discontinuation, physical distress, lack of energy, and depression are distress, lack of energy, and depression are reported. reported. Long periods of use may lead to memory Long periods of use may lead to memory loss, difficulties with speech and thinking, loss, difficulties with speech and thinking, depression, and weight loss. depression, and weight loss.

OD TreatmentOD Treatment

OD OD -- No antidoteNo antidotePossible 5Possible 5--10 mg diazepam (IV)10 mg diazepam (IV)Haloperidal or chlorpromazineHaloperidal or chlorpromazine--PsychosisPsychosisMonitor airway Monitor airway vsvs respiratory arrestrespiratory arrestBody temperature > 105Body temperature > 105ooFFHypertension in 50% casesHypertension in 50% casesViolent behaviorViolent behavior

Methods of AnalysisMethods of Analysis

Screening techniquesScreening techniquesRIA, EMIT, ELISA, TLC, etc.RIA, EMIT, ELISA, TLC, etc.

Confirmation Confirmation SPESPE vsvs LiqLiq././LiqLiq..GC/MS, GC/NPD, GC/MS/MS, LC/MS, GC/MS, GC/NPD, GC/MS/MS, LC/MS,

etc.etc.

ELISA ScreeningELISA ScreeningImmunalysis Immunalysis PCP Direct ELISA KitPCP Direct ELISA Kit

Tecan MinilyserTecan Minilyser

100 100 ulul sample size diluted 1/10 up to 1 mlsample size diluted 1/10 up to 1 ml

2.5 ng/ml = PCP cut off 2.5 ng/ml = PCP cut off

Extraction MethodExtraction Method33--ml sample sizeml sample sizeDD5- Phencyclidine (IS)Phencyclidine (IS)Zinc Sulfate to precipitateZinc Sulfate to precipitateUCT UCT –– DAU SPE columnsDAU SPE columnsRinse with Sodium Acetate Buffer, Acetic Rinse with Sodium Acetate Buffer, Acetic Acid, Acid, MeOH MeOH Elute w/ Dichloromethane : Elute w/ Dichloromethane : Isopropanol :TrimethylamineIsopropanol :TrimethylamineReconstitute w/ Ethyl AcetateReconstitute w/ Ethyl Acetate

Instrument Info.Instrument Info.

AgilentAgilent GC/MS 6890/5973GC/MS 6890/5973HPHP--5 Capillary Col. 5 Capillary Col. 15m x 0.25mm x0.25 15m x 0.25mm x0.25 µµmm

Injector Temp 260Injector Temp 260°°CCDetector Temp 300Detector Temp 300°°CC180180°°C to 200C to 200°°C @ 10C @ 10°°C/minC/min200200°°C to 300C to 300°°C for burnoutC for burnout

5ng/ml of PCP + 67 ng/ml of D5 PCP

Fatal PCP LevelsFatal PCP Levels

17 deaths due to acc/intentional 17 deaths due to acc/intentional ingestion ingestion ((BaseltBaselt 66thth ed.)ed.)

Blood Liver Urine Gastric ug/ml ug/g ug/ml mg

Avg 4.8 23 35 155Range (0.3 – 25) (.9-170) (0.4-120) (0-840)

LA CoronerLA CoronerPCP Summary 2000PCP Summary 2000--20012001

2000-2001 Mode of Death No. of Cases Range Average Range Average (# of Cases)

Homicide 85 * 17-56 29 3.1-870 129 (68)Accident 38 0-52 37 1.8-1,070 251 (32)Suicide 4 21-30 24 13-498 225 (4)Natural 4 35-49 41 38-59 31 (2)

Undetermined 3 23-44 35 37-84 61 (2)Total 134

Age Central Blood PCP Levels (ng/ml)

*Note: 79 of 85 homicides were due to a Gunshot Wound.

Year 2000: 5,040 Cases received for Toxicological analysisYear 2001: 5,392 Cases received for Toxicological analysis

Confirmed Positive PCP rate: 134/10,432 or 1.3%

LA CoronerLA CoronerPCP Summary 2002PCP Summary 2002

Confirmed Positive PCP rate: 104/5,167 or 2.0%Note: 54 of 57 homicidies were due to a GSW

2002 Mode of Death No. of Cases Range Average Range Average (# of Cases)

Homicide 57 15-53 26 2.6-564 104 (54)Accident 42 19-78 41 2-3620 321 (34)Suicide 5 23-47 35 135-427 288 (4)Natural 3 31-50 43 8.5-583 229 (3)

Undetermined 0 0 0 0 0Total 104


LA CoronerLA CoronerPCP Summary 2003PCP Summary 2003

Confirmed Positive PCP rate: 74/5058 or 1.4%Note: 40 of 42 homicides were due to a GSW

2003 Mode of Death No. of Cases Range Average Range Average (# of Cases)

Homicide 42 13-58 27 2.9-734 99 (38)Accident 26 23-53 42 5.5-799 191 (32)Suicide 4 27-59 41 65-838 359 (3)Natural 0 0 0 0 0

Undetermined 2 33-37 35 106-197 152 (2)Total 74


LAPD DUILAPD DUI

Year

Total PCP screens

Positive Samples

% Positive

1998 4498 156 3.51999 3435 139 4.02000 2317 133 5.72001 1785 93 5.22002 1895 111 5.92003 2325 92 4.0

DUI LevelsDUI Levels

Pearce 1976 Kunsman et al. 1997 LAPD unpublished

ng/ml ng/ml ng/ml Range 7 - 240 12 - 118 10 - 118 Avg. 75 51 58

Subjects 26 56 28

Case #1 Case #1 –– It It ain’tain’t waterwater

37 y/o 37 y/o AfAf. Amer. Male . Amer. Male –– well nourishedwell nourished171 lbs171 lbs 71 inches71 inches

1400 hrs 1400 hrs -- Friends over for a drinkFriends over for a drink1900 hrs 1900 hrs –– Wife asked friends to leaveWife asked friends to leave0100 hrs 0100 hrs –– Dec. drove out with friends Dec. drove out with friends

to smoketo smoke

Case #1 Case #1 –– ItIt ain’tain’t waterwater0600 hrs 0600 hrs –– Friends drag Dec. into house Friends drag Dec. into house

to perform CPRto perform CPRPronounced at Antelope Valley HospitalPronounced at Antelope Valley Hospital

AutopsyAutopsyLimitedLimitedHospital caseHospital case

ToxicologyToxicologyPending HPending H--screenscreen

Case #1 Case #1 –– ItIt ain’tain’t waterwater

20 y/o 20 y/o HxHx of Alcohol & Drug Abuseof Alcohol & Drug Abuse

Supposedly drank 10 40 oz. Malt LiquorSupposedly drank 10 40 oz. Malt Liquor(Old English 1800) and a bottle of gin(Old English 1800) and a bottle of gin

Friends saying “Brother Rude, he drank Friends saying “Brother Rude, he drank some ‘water’”some ‘water’”


PCP Etoh ng/ml g%

Heart Blood 3,620 0.18

Femoral Blood 5,900 0.19


Mode = AccidentMode = Accident

CoDCoD = Toxicity from Ethanol & PCP= Toxicity from Ethanol & PCP

Case #2Case #2--Age don’t matter!Age don’t matter!

78 y/o Hispanic Male78 y/o Hispanic Male

150 lbs 150 lbs 65 inches65 inches

Found unresponsive over a vehicleFound unresponsive over a vehicle

Pronounced at Whittier HospitalPronounced at Whittier Hospital


HxHx of IVDA for heroinof IVDA for heroinOD’d on heroin in his early 70’sOD’d on heroin in his early 70’s

AutopsyAutopsyLimitedLimitedHospital caseHospital case

ToxicologyToxicologyPendingPending


PCP Amp. Meth. ng/ml ug/ml ug/ml

Heart Blood ND 0.03 0.55Urine 8.7


Mode = AccidentMode = Accident

CoDCoD = = AAtherosclerotic cardiovascular therosclerotic cardiovascular disease disease

Case #3 Case #3 –– Flunking LabFlunking Lab

45 y/o & 36 y/o 45 y/o & 36 y/o AfAf.. AmerAmer Males Males

231 lbs231 lbs 248 lbs248 lbs72 inches72 inches 73 inches73 inches


Overcome by fumes in eveningOvercome by fumes in evening

Hosed downHosed down

Dropped off at hospitalDropped off at hospital

Pronounced deadPronounced dead


AutopsyAutopsySlightly sweet aromatic odorSlightly sweet aromatic odor

Feeling dizzyFeeling dizzy

ToxicologyToxicologyPending CPending C--screens & Volatiles screens & Volatiles -- EtherEther


Both decedents had ethyl ether in their Both decedents had ethyl ether in their bloodbloodBoth had PCPBoth had PCPCase Case HxHx suggested PCP synthesis suggested PCP synthesis gone badgone badLooked for cyanideLooked for cyanide


45 y/o45 y/oPCP Etoh Ethyl Ether Cyanide ng/ml g% ug/ml

Heart 5.5 0.12 + 1.7Femoral 0.09 + QNS Vitreous ND

Urine +<5.0


36 y/o36 y/o

PCP Etoh Ethyl Ether Cyanide Coc. ng/ml g% ug/ml ug/ml

Heart 72 0.12 + 2.7 0.11Femoral 0.2 + 3.1


Mode = Accidental DeathsMode = Accidental Deaths

CoD CoD = Cyanide Toxicity= Cyanide Toxicity

Case #4: “Hannibal”Case #4: “Hannibal”

Gruesome Homicide of a Gruesome Homicide of a 21 y/o 21 y/o AfAf. Amer. Female. Amer. FemaleThe Cast:The Cast:

AntronAntron “Big Lurch” Singleton“Big Lurch” SingletonTynisha YsaisTynisha YsaisThomas MooreThomas MooreAlisa AllenAlisa Allen“Doc”“Doc”

Victim’s ResultsVictim’s ResultsAssaulted with multiple instrumentsAssaulted with multiple instrumentsMajor trauma to the face and torsoMajor trauma to the face and torsoLungs were eatenLungs were eatenSpermatozoa was detected but not profiled Spermatozoa was detected but not profiled from female sexual assault kitfrom female sexual assault kit

PCPPCPHeart BloodHeart Blood 6.2 ng/ml6.2 ng/ml

Defendant’s ResultsDefendant’s Results

Arrested 4/10/02 ~1300 hrsArrested 4/10/02 ~1300 hrs PCPPCPngng/ml/ml

Sampled 4/11/02 1115 hrsSampled 4/11/02 1115 hrs BloodBlood 10 10 Samples 4/11/02 2245 hrsSamples 4/11/02 2245 hrs UrineUrine 2626

The RulingThe Ruling

June 25, 2003June 25, 2003TwoTwo--week trial, the fiveweek trial, the five--man, sevenman, seven--woman jury foundwoman jury found AntronAntron Singleton, 26, Singleton, 26, guiltyguilty of firstof first--degree murder and degree murder and guiltyguiltyof aggravated mayhem and also found of aggravated mayhem and also found true the special circumstance of true the special circumstance of inflicting torture on the victiminflicting torture on the victim

Sanity?Sanity?July 1, 2003July 1, 2003

Compton Superior Court judge issued a Compton Superior Court judge issued a directed verdict of directed verdict of sanesaneUnder state law passed in 1993Under state law passed in 1993--94 (Section 94 (Section 25.5 of the California Penal Code), a 25.5 of the California Penal Code), a defendant may not use a defense of not guilty defendant may not use a defense of not guilty by reason of insanity if the mental illness is by reason of insanity if the mental illness is caused by drug addiction or drug abuse.caused by drug addiction or drug abuse.

ConclusionsConclusions

Involved in violent/traumatic deathsInvolved in violent/traumatic deaths

Mechanism of action not wellMechanism of action not wellunderstoodunderstood

PCP is still an abused drugPCP is still an abused drug

AcknowledgementsAcknowledgements

Dr. Paul Dr. Paul Gliniecki Gliniecki Drew Drew Josfan Josfan Todd Todd SwantonSwantonCoroner Coroner –– Lab Personnel Lab Personnel

ReferencesReferencesBaselt RC. Disposition of Toxic Drugs and Chemicals in Man 6th ed.,Biomedical Publications: Foster City; 2002Ellenhorn M, Barceloux D: Medical Toxicology: Diagnosis and Treatment of Human Poisoning, Elsevier: New York; 1988Jenkins, A: Hallucinogens; in Levine B (ED): Principles of Forensic Toxicology; AACC Press: Washington, DC; 1999Kuhn, Cynthia, Scott Swartzwelder and Wilkie Wilson. Buzzed : the straight facts about the most used and abused drugs from alcohol to ecstasy. New York: W.W. Norton, 1998.Kunsman GW, Levine B, Costantino A, Smith ML. Phencyclidine blood concentrations in DRE cases. J Anal Tox 1997;21(6):498-502.Mozayani A: Phencyclidine – Effects on human performance and behavior; Forensic Sci Rev 15:61;2002."PCP" Britannica.com. Vers. 20011999-2001. Encyclopædia Britannica.Pearce D: Detection and quantitation of phencyclidine in blood by use of (2H5)phencyclidine and select ion monitoring applied to nonfatal cases of phencyclidine intoxication; Clin Chem 22:1623; 1976

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