GHB - cal tox · California Poison Control System - San Francisco Division GHB Abuse, Addiction & Assault Jo Ellen Dyer, PharmD California Poison Control System Associate

California Poison Control System - San Francisco Division

GHBGHBAbuse, Addiction & AssaultAbuse, Addiction & Assault

Jo Ellen Dyer, Jo Ellen Dyer, PharmDPharmD

California Poison Control SystemCalifornia Poison Control SystemAssociate Clinical ProfessorAssociate Clinical Professor

University of California San FranciscoUniversity of California San Francisco


•• Poisoning and drug overdose consultsPoisoning and drug overdose consults–– Public Public –– Healthcare practitionersHealthcare practitioners

•• California coverage for ~34 millionCalifornia coverage for ~34 million–– 800 800 –– 1000 calls per day1000 calls per day–– Access 24 hours a day, 7 days a weekAccess 24 hours a day, 7 days a week

•• Toll free access Toll free access –– CA 800CA 800--876876--4766 4766 –– U.S. 800U.S. 800--222222--12221222

•• Regional poisoning focused surveillanceRegional poisoning focused surveillance


Trends in GHB UseTrends in GHB Use

•• 19601960 Synthesized in France: anesthetic Synthesized in France: anesthetic •• 19891989 Anabolic steroids Anabolic steroids Controlled substance U.S.Controlled substance U.S.•• 19901990--91 91 BodybuildingBodybuilding•• 19921992--93 93 Sleep aid, dieting / Europe alcohol withdrawalSleep aid, dieting / Europe alcohol withdrawal•• 19941994 DSHEA: alleged dietary supplementDSHEA: alleged dietary supplement•• 19951995 Raves / Analysis developed / fatalities reportedRaves / Analysis developed / fatalities reported•• 19961996 Sexual enhancer, “dateSexual enhancer, “date--rape” drugrape” drug

Dependence & withdrawal syndrome identified Dependence & withdrawal syndrome identified •• 19971997 CC--II in California, Analogs: GBL, BD use II in California, Analogs: GBL, BD use ��•• 20002000 US CUS C--I, GBL list I; New analogs? Solvents?I, GBL list I; New analogs? Solvents?•• 20022002 Xyrem Xyrem -- FDA Approved, C III for medical useFDA Approved, C III for medical use


GHBGHB

•• AbuseAbuse•• AddictionAddiction•• FatalitiesFatalities•• AssaultAssault


WHY Use GHB??WHY Use GHB??

•• Miotto Miotto et al 2001 n = 42, interviewet al 2001 n = 42, interview–– What do you want to achieve?What do you want to achieve?–– Increase in: wellIncrease in: well--being, sexual arousal, being, sexual arousal,

sociability, and the high of other drugs, sociability, and the high of other drugs, also to sleep.also to sleep.

•• Degenhardt Degenhardt et al 2002, n = 76, interviewet al 2002, n = 76, interview–– Best things about using GHB?Best things about using GHB?–– Euphoria, aphrodisiac, sociability, lose Euphoria, aphrodisiac, sociability, lose

inhibitions, relax, cheapinhibitions, relax, cheap, ,


GHB Exposures GHB Exposures CPCSCPCS & & DAWNDAWN

18 10 934

1937

89105

356 365

282

172

74

232

199

0

50

100

150

200

250

300

350

400

1990

California Poison Control California Poison Control Statewide 32Statewide 32--34 million34 million

San Francisco Poison ControlSan Francisco Poison ControlBay Area 7Bay Area 7--8 million8 million

DAWN Office of Applied Studies, SAMHSADAWN Office of Applied Studies, SAMHSA


GHB AbuseGHB Abuse22 year old female brought in by ambulance from 22 year old female brought in by ambulance from

SOMA dance club after vomiting, then abruptly SOMA dance club after vomiting, then abruptly loosing consciousness, loosing consciousness,

Enroute myoclonic Enroute myoclonic jerking was observedjerking was observedExam: GCS 3, periods of apnea, Pupils 4Exam: GCS 3, periods of apnea, Pupils 4mmmm

VS: VS: HR 50, BP 100/70, RR 8, T 35 BS+HR 50, BP 100/70, RR 8, T 35 BS+Field care: Field care: intubation, intubation, narcan narcan 2mg 2mg -- no responseno response

Fingerstick Fingerstick glucose 80mg/dl glucose 80mg/dl ABGABG: pH 7.35, PCO: pH 7.35, PCO22 42, PO42, PO22 261261


GHB AbuseGHB Abuse

Admitted to ICU on ventilator, Became agitated Admitted to ICU on ventilator, Became agitated as level of consciousness increased as level of consciousness increased

2 hours after arrival 2 hours after arrival -- selfself--extubated extubated 4 hours GCS 154 hours GCS 15Laboratories: Blood alcohol < 10Laboratories: Blood alcohol < 10Urine screen Urine screen negneg: amphetamine, cocaine, opiates, : amphetamine, cocaine, opiates,

barbiturates, benzodiazepines, PCP, THCbarbiturates, benzodiazepines, PCP, THCGHB: Blood 91mg/l; urine 572mg/lGHB: Blood 91mg/l; urine 572mg/l


88 GHB Overdoses Over 3 Years @ SFGH88 GHB Overdoses Over 3 Years @ SFGH

Male: 69%Male: 69% Age: 18 Age: 18 -- 51 51 33% no co33% no co--ingestion ingestion CoCo--ingestion 67% ingestion 67% Multiple coMultiple co--ingestion 13%ingestion 13%

•• Coma Coma GCS: 28%=3, 33%=4GCS: 28%=3, 33%=4--8 8 •• MyoclonusMyoclonus•• Bradycardia Bradycardia (HR <55 BPM)(HR <55 BPM)

•• Hypotension 11%Hypotension 11%•• Resp Resp acidosis acidosis (PCO2 >45, pH 7.24(PCO2 >45, pH 7.24--7.34)7.34)

•• Depressed gag, VomitingDepressed gag, Vomiting•• Hypothermia, T < 35°CHypothermia, T < 35°C•• Emergence Emergence -- delirium, combativedelirium, combative

Ethanol Ethanol 3434 MDMA 12 Heroin 2 SedativeMDMA 12 Heroin 2 Sedative 2 2 Amphetamine Amphetamine 15 15 Cocaine 4 MJ Cocaine 4 MJ 2 LSD 2 LSD 11

Chin et al. Chin et al. AnnEmergMed AnnEmergMed 1998 (19931998 (1993--1996)1996)


Why patient variability?Why patient variability?

•• Clandestine laboratory productionClandestine laboratory production–– Variable purity and concentrationVariable purity and concentration

•• Narrow therapeutic indexNarrow therapeutic index–– Doubling a therapeutic dose may cause comaDoubling a therapeutic dose may cause coma

•• BioavailabilityBioavailability–– 36% higher absorption on empty stomach 36% higher absorption on empty stomach

•• Genetic VariabilityGenetic Variability–– Eg: GHB, BD and alcohol/aldehyde dehydrogenaseEg: GHB, BD and alcohol/aldehyde dehydrogenase

•• Drug InteractionsDrug Interactions–– Eg: Ethanol , depressantsEg: Ethanol , depressants


Gamma Hydroxybutyrate (Gamma Hydroxybutyrate (GHBGHB) Analogs ) Analogs Gamma Butyrolactone (Gamma Butyrolactone (GBLGBL) and 1,4) and 1,4--Butanediol (Butanediol (BDBD) )

NaOH + H2Oin vitro

in vivoLactonase

Alcoholdehydrogenase

Aldehydedehydrogenase

GHBGHB

GBL

BDBD

GHBGHB

GHBGHB


GHB and Analog ProductsGHB and Analog ProductsGamma Butyrolactone Gamma Butyrolactone (GBL)(GBL) & 1,4& 1,4--Butanediol Butanediol (BD)(BD)

GammaGamma--OH OH Somatomax Somatomax PMPMAlcoverAlcover Gamma HydrateGamma HydrateXyremXyrem Natural Sleep 500Natural Sleep 500

GHB

GBL

BD

Blue Nitro 2.5gm/ozInvigorate 3.5gm/ozGH Gold 34gm/ozRenewTrient 1.98gm/6

Zen 4gm/oz Rejoov 3gm/ozInner G 2.25gm/oz


The authentic herbal wineThe authentic herbal wine The fake wine is GBLThe fake wine is GBL


Available on the Internet Available on the Internet 11--1717--20042004

QuickTime™ and aTIFF (Uncompressed) decompressor

are needed to see this picture.


GHB WithdrawalGHB Withdrawal

23 year old female student & 23 year old female student & bodybuilder, took 3bodybuilder, took 3--5 “5 “capsfullcapsfull” ” of liquid GHB daily for a year for of liquid GHB daily for a year for the purported anabolic effects. the purported anabolic effects.

Six weeks prior to admission she Six weeks prior to admission she increased her dosing frequency to increased her dosing frequency to every 3 hours A.T.C. to prevent every 3 hours A.T.C. to prevent the anxiety, tremors and insomnia the anxiety, tremors and insomnia she experienced without GHB.she experienced without GHB.


GHB WithdrawalGHB Withdrawal

Admission Admission detox detox center: center: Combative Combative Paranoid, visual & auditory hallucinationsParanoid, visual & auditory hallucinations

VS: VS: HR 110, BP 138/98, T 98.5, HR 110, BP 138/98, T 98.5, GGT GGT 22, 22, UtoxUtox: : negnegWithdrawal course 9 days:Withdrawal course 9 days:

Agitated, delirious, Agitated, delirious, tachycardic tachycardic & hypertensive& hypertensive6 month follow up 6 month follow up -- AsxAsx, no meds, GPA 4.0, no meds, GPA 4.0

GHB sample 721 mg/ml (3.6 gm/capful)GHB sample 721 mg/ml (3.6 gm/capful)Dose Maximum 144 gm/dayDose Maximum 144 gm/day

Dyer and Andrews, J Toxicol Clin Toxicol 1997


GHB Addiction Series GHB Addiction Series •• Age: 22Age: 22--38 Sex: M 75%, F 25%38 Sex: M 75%, F 25%•• Reason: bodybuilding 63% Reason: bodybuilding 63% •• Employed or student: 88%Employed or student: 88%•• Dose: 43 Dose: 43 --144 gm/day, q1144 gm/day, q1--3 hr A.T.C., 3 hr A.T.C., 2 mo2 mo--3 yr3 yr•• Onset 1Onset 1-- 6 hours after last dose 6 hours after last dose

–– Insomnia, tremor, anxiety, diaphoresisInsomnia, tremor, anxiety, diaphoresis•• Progression over 1Progression over 1--3 days3 days

–– Agitation, Agitation, dysphoriadysphoria, delirium, hallucinations , delirium, hallucinations –– Tachycardia, hypertensionTachycardia, hypertension

•• Duration 5Duration 5--15 days 15 days -- episodic symptomsepisodic symptomsDyer, Roth and Dyer, Roth and HymaHyma. . AnnEmergMed AnnEmergMed 20012001


D.U.I. GHB September 11, 2002D.U.I. GHB September 11, 2002


GHB Related FatalitiesGHB Related Fatalities•• DEA count 71 GHBDEA count 71 GHB--related death 3/2000related death 3/2000•• Project GHB website >260Project GHB website >260•• Small studySmall studyAutopsy & investigative reports obtained Autopsy & investigative reports obtained

from state medical examiners and coroners from state medical examiners and coroners by written requestby written request

20 cases were reviewed for20 cases were reviewed for–– Demographic featuresDemographic features–– Toxicological resultsToxicological results–– Pathologic findingsPathologic findings

Dyer JE, Haller CA. Dyer JE, Haller CA. J J Toxicol Clin ToxicolToxicol Clin Toxicol. 2001;39(5):518. 2001;39(5):518


GHB Accidental FatalityGHB Accidental Fatality

Age YearsAge Years EthanolEthanol GHBGHB28 male28 male hot tubhot tub 40mg/dl40mg/dl 160mg/l160mg/l

Cause: Cause: Drowning Drowning Alcohol + GHB intoxicationAlcohol + GHB intoxication

29 female29 female chin to chestchin to chest 170mg/l170mg/lCause:Cause: Probable Idiopathic cardiac arrhythmiaProbable Idiopathic cardiac arrhythmia

GHB intoxicationGHB intoxication15 male15 male desert ravedesert rave 375mg/l375mg/l

Cause: Cause: GHB intoxication, hypothermiaGHB intoxication, hypothermia


Cause of DeathCause of Death•• Deaths result from respiratory compromise, Deaths result from respiratory compromise,

supporting need for prompt airway supporting need for prompt airway management management

•• Abrupt loss of consciousness may results in Abrupt loss of consciousness may results in traumatic injury or accidenttraumatic injury or accident

•• Drug intoxication: 15 casesDrug intoxication: 15 cases•• CardioCardio--respiratory arrest: 3 casesrespiratory arrest: 3 cases•• DrowningDrowning•• Idiopathic cardiac arrhythmiaIdiopathic cardiac arrhythmia•• Hypovolemic Hypovolemic shockshock


20 GHB20 GHB--Related FatalitiesRelated FatalitiesAge: Age: 15 15 -- 46 years46 years Sex:Sex: Male 75% Female 25%Male 75% Female 25%

Toxicology : Toxicology : No coNo co--ingestion 20%ingestion 20%60% Ethanol [0.0160% Ethanol [0.01--0.17%]0.17%]10% THC, MDMA, Cocaine, Caffeine 10% THC, MDMA, Cocaine, Caffeine 5% 5% MethamphetMethamphet, , ButalbitalButalbital, , VenlafaxineVenlafaxine, APAP, APAP

GHB Levels:GHB Levels:Blood Blood 140 140 -- 2,900 mg/l2,900 mg/lUrineUrine 305 305 -- 27,000 mg/l27,000 mg/l

Physical Findings:Physical Findings:Pulmonary edema Pulmonary edema 80%80%Cardiomegaly Cardiomegaly LVHLVH 35%35%Aspiration Aspiration 20%20%

Dyer and Haller, J Dyer and Haller, J Toxicol Clin Toxicol Toxicol Clin Toxicol 20012001


Post Mortem GHB AnalysisPost Mortem GHB AnalysisGHBGHB--related fatalities postrelated fatalities post--mortem (pm) mortem (pm)

–– Blood [140Blood [140--2,900 mg/l] Urine [3052,900 mg/l] Urine [305--27,000 mg/l]27,000 mg/l]96 non96 non--GHBGHB--pm, pm, 13 13 --71 days pm 71 days pm

–– GHB Blood femGHB Blood fem 1.7 1.7 -- 48 mean 11 mg/l48 mean 11 mg/l–– GHB UrineGHB Urine 0 0 -- 14 mean 4.6 mg/l14 mean 4.6 mg/l

Anderson. CA AssocAnderson. CA Assoc Tox Tox 1997199720 non20 non--GHBGHB--pm, 75% positive pm, 75% positive

–– GHB BloodGHB Blood 3.2 3.2 -- 168 mean 25 mg/l168 mean 25 mg/l–– GHB UrineGHB Urine negativenegative

FielerFieler. . Clin Chem Clin Chem 1998 44(3):6921998 44(3):69245 non45 non--GHBGHB--pm, 80% positive pm, 80% positive

–– GHB bloodGHB blood 1 1 -- 49 mean 24 mg/l49 mean 24 mg/lPan. AAFS Proceedings 1999:271Pan. AAFS Proceedings 1999:271

AntiAnti--mortem nonmortem non--GHB blood & urine < 10 mg/lGHB blood & urine < 10 mg/l


Drug Facilitated Sexual Drug Facilitated Sexual AssaultAssault


Sturman Sturman Report, England 2000Report, England 2000

123 victims: a self123 victims: a self––selected sampleselected sample•• Venue: 50% clubs, public housesVenue: 50% clubs, public houses•• Attack venue: 71% residence, 21% hotelAttack venue: 71% residence, 21% hotel•• Association: 70% not strangersAssociation: 70% not strangers

–– Friends, colleagues, students, neighbors, partnersFriends, colleagues, students, neighbors, partners•• Memory: 20% no memoryMemory: 20% no memory•• Realize attack: 84% within 24 hoursRealize attack: 84% within 24 hours•• Convinced of attack: 1/3 by memory aloneConvinced of attack: 1/3 by memory alone

–– 72% with injuries, physical evidence72% with injuries, physical evidence•• Methods: alcohol 54%, soft drink 19%Methods: alcohol 54%, soft drink 19%


Drug Facilitated AssaultDrug Facilitated Assault

42 year old F with co42 year old F with co--workers after workworkers after work2200 2200 BeerBeer24002400 MargaritaMargarita01000100 Ride to car with coRide to car with co--workersworkers

Last memory taking a drink of “salty water”Last memory taking a drink of “salty water”05000500 Next memory awake unable to move Next memory awake unable to move

Stumbled out of residence, called 911 Stumbled out of residence, called 911 Investigator recognized symptoms, to EDInvestigator recognized symptoms, to ED

Tox result: B.A. 0.01%, U. tox: GHB 424 mg/lTox result: B.A. 0.01%, U. tox: GHB 424 mg/lReported immediatelyReported immediatelyAlcohol kinetically accurate with timeAlcohol kinetically accurate with time

2000 CA Superior Court2000 CA Superior Court


DFSA 22 Prosecuted IncidentsDFSA 22 Prosecuted Incidents•• 22 criminally prosecuted incidents22 criminally prosecuted incidents•• 13 convictions or plea admissions 60% 13 convictions or plea admissions 60% •• 9 acquittals9 acquittals

–– One civil conviction, award $5 millionOne civil conviction, award $5 million

•• Victim’s ages ranged 16 Victim’s ages ranged 16 -- 44 years44 years•• Assailant’s ages ranged 17 Assailant’s ages ranged 17 -- 45 years45 years•• Toxicology analysis of biologic specimen Toxicology analysis of biologic specimen

–– 9 incidents, sampled 69 incidents, sampled 6--120 hours after120 hours after–– 6 convicted6 convicted 3 acquitted3 acquitted


INGESTED SUBSTANCESINGESTED SUBSTANCES

GHB involvement certain in 7 incidentsGHB involvement certain in 7 incidents–– GHB 424 mg/l in urine at 6 hoursGHB 424 mg/l in urine at 6 hours–– 6 other incidents GHB used6 other incidents GHB used

•• 11-- Voluntary ingestion GHBVoluntary ingestion GHB•• 22-- Ingestion new nutritional to feel better Ingestion new nutritional to feel better •• 11-- Liquid X on pretext phoneLiquid X on pretext phone•• 22-- Admitted in plea for manufacture and salesAdmitted in plea for manufacture and sales

•• CoCo--ingestions detectedingestions detected–– THC, cocaine, ethanol, THC, cocaine, ethanol, diphenhydraminediphenhydramine


Toxicology Considerations Toxicology Considerations •• Toxicology results not the only evidenceToxicology results not the only evidence

–– Rarely provides significant evidenceRarely provides significant evidence

•• Urine longer duration detection, <3Urine longer duration detection, <3--4 days4 days–– Blood concentrations with pharmacokinetics can Blood concentrations with pharmacokinetics can

estimate time and concentration, < 24 hoursestimate time and concentration, < 24 hours

•• Negative: does not rule out drug ingestionNegative: does not rule out drug ingestion–– Substance not included in screenSubstance not included in screen

Amp, Amp, CocCoc, OP, PCP, THC, Barb, , OP, PCP, THC, Barb, BzpBzp–– Drug eliminated below detection limitDrug eliminated below detection limit

•• Positive: not always surreptitiously usedPositive: not always surreptitiously used–– Voluntary ingestion is not consent for assaultVoluntary ingestion is not consent for assault–– Potentiated Potentiated effects from other depressantseffects from other depressants


Drug Rapist ProfileDrug Rapist Profile•• Age: 30Age: 30--7070•• Presentable: Presentable: attractive, confident, influential attractive, confident, influential

•• Claims consent: Claims consent: deny & in denial deny & in denial

•• Shifts blame to victimShifts blame to victim•• Souvenirs: Souvenirs: photos or videos, trophies, trinketsphotos or videos, trophies, trinkets

–– rarely cash, jewelry, credit cardsrarely cash, jewelry, credit cards

•• Serial predator: Serial predator: refines tactics as progressesrefines tactics as progresses

•• Groups of offenders: Groups of offenders: including F. accomplicesincluding F. accomplices

•• Opportunist: Opportunist: preys onpreys on voluntarily incapacitatedvoluntarily incapacitated


•• Drug effects Drug effects –– Dose response, timeDose response, time--course, interactionscourse, interactions

•• Narrow the field of suspected drugs, rarelyNarrow the field of suspected drugs, rarely–– Time Time -- course, symptoms course, symptoms

•• Direct biologic sample analysisDirect biologic sample analysis–– Time of possible detection, fluid neededTime of possible detection, fluid needed

•• Describe changing forms, availabilityDescribe changing forms, availability•• ID inconsistent symptoms or quell doubtsID inconsistent symptoms or quell doubts

How can a Toxicologist help? Investigation?How can a Toxicologist help? Investigation?


TestimonyTestimony•• Explain lab results positive and negativeExplain lab results positive and negative

–– Screenable Screenable drug? Within detection time & limit?drug? Within detection time & limit?•• Inform jury of typical effects of assault drugsInform jury of typical effects of assault drugs•• Predict course & drug effects on victimPredict course & drug effects on victim

–– Using body weight, known coUsing body weight, known co--ingestionsingestions–– Onset, peak, duration of effectOnset, peak, duration of effect

•• Calculate blood alcohol levels Calculate blood alcohol levels -- voluntary use voluntary use –– Volume ingested, effects and time courseVolume ingested, effects and time course

•• Provide framework for victim recollections Provide framework for victim recollections –– Typical timeTypical time--course, physical, psychological effectcourse, physical, psychological effect


Nationwide Investigation ofNationwide Investigation of DFSA DFSA Focus on Cases With Documented GHBFocus on Cases With Documented GHB

Victim Interview StudyVictim Interview Study

Email: Email: [email protected]@itsa.ucsf.edu with contact with contact information for DA’s, Investigators or information for DA’s, Investigators or

Toxicologists regarding casesToxicologists regarding cases


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FACTORS IN OVERDOSE RESEARCH INTO GHB EFFECTS

GHB USE: MOTIVATIONS, MEDICAL CONSEQUENCES AND RISKS

Grant support:Grant support: NIDA NIDA DA 14935DA 14935

Documents

GHB - cal tox · California Poison Control System - San Francisco Division GHB Abuse, Addiction & Assault Jo Ellen Dyer, PharmD California Poison Control System Associate