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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
Age Central Blood PCP Levels (ng/ml)
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
Age Central Blood PCP Levels (ng/ml)
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’”
Case #1 Case #1 –– ItIt ain’tain’t waterwater
PCP Etoh ng/ml g%
Heart Blood 3,620 0.18
Femoral Blood 5,900 0.19
Case #1 Case #1 –– ItIt ain’tain’t waterwater
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
Case #2Case #2--Age don’t matter!Age don’t matter!
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
Case #2Case #2--Age don’t matter!Age don’t matter!
PCP Amp. Meth. ng/ml ug/ml ug/ml
Heart Blood ND 0.03 0.55Urine 8.7
Case #2Case #2--Age don’t matter!Age don’t matter!
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
Case #3 Case #3 –– Flunking LabFlunking Lab
Overcome by fumes in eveningOvercome by fumes in evening
Hosed downHosed down
Dropped off at hospitalDropped off at hospital
Pronounced deadPronounced dead
Case #3 Case #3 –– Flunking LabFlunking Lab
AutopsyAutopsySlightly sweet aromatic odorSlightly sweet aromatic odor
Feeling dizzyFeeling dizzy
ToxicologyToxicologyPending CPending C--screens & Volatiles screens & Volatiles -- EtherEther
Case #3 Case #3 –– Flunking LabFlunking Lab
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
Case #3 Case #3 –– Flunking LabFlunking Lab
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
Case #3 Case #3 –– Flunking LabFlunking Lab
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
Case #3 Case #3 –– Flunking LabFlunking Lab
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