Club Drugs: MDMA, Ketamine and GHB

Teri Martin

teri.martin@jus.gov.on.ca

November 25, 2003

Outline

• Overview of rave culture and “club drugs”

• MDMA, Ketamine, GHB• Appearance and availability

• Pharmacology and toxicology

• Interpretation issues

• Drug facilitated sexual assault

• Role of toxicology in the DFSA investigation

Rave Culture

• Historically marathon dance parties

• Techno music (120-140 bpm)

• Held in secret: warehouses, clubs, outdoors

• High school/college age students

• 3 common themes: music, people, drugs

• Peace Love Unity Respect

• Face of raves has changed but the “dance music community” remains – drug use persists

MDMAMethylenedioxymethamphetamineEcstasy, XTC, Adam, Hug-drug, “X”, M+M

MDMA

• Sympathomimetic and hallucinogenic

• “Designer” derivative of methamphetamine

• Past, legitimate uses:• Appetite suppressant

• Adjunct to psychotherapy

CH3

NH CH3

CH3

NH CH3

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MDMA: Availability

• Clandestine synthesis – primarily in Europe, with some manufacture occurring in Canada and the U.S.

• In 2001, 62% of high school seniors stated MDMA would be “fairly easy” or “very easy” to obtain

• Since 1998, MDMA consumption among U.S. teenagers doubled. Use of other illicit drugs remains unchanged.

• 6% of Toronto students reported using Ecstasy in 2000. Compare to 1991 where less than 1% of students reported use of the drug.

MDMA: Pharmacology

• Mechanism: presence of neurotransmitters• Increased release of serotonin, dopamine, norepinephrine• Inhibition of metabolism

• Administration is typically oral (50 – 150 mg)

• Onset of effects within 30 minutes

• Peak effects within 1-1.5 hours

• Duration of effects average 3-4 hours

• Active metabolite MDA

MDMA: Desired effects

• Euphoria and benevolence

• Feelings of closeness to others

• Talkativeness

• Desire to interact

• Enhanced perception

• Mild hallucinogenic effects

MDMA: Unpleasant effects

Immediate effects: palpitations sweating teeth-grinding jaw-clenching

Delayed effects: drowsiness muscle aches irritability

MDMA Toxicity

1. Hepatic toxicity

2. Cardiac toxicity

3. Cerebral edema

4. Hyperthermia*

MDMA: Hepatic Toxicity

• Jaundice frequently reported in individuals suffering from MDMA intoxication:

• Adulterants in MDMA tablets• Secondary to hyperthermia• Depletion of glutathione during metabolism

• Liver transplantation may be required in severe cases

MDMA: Cardiac Toxicity

• Sympathomimetic ( norepinephrine)

• Hypertension

• Tachycardia

• Arrhythmia

• Increased cardiac workload

• Stroke, hemorrhage, heart failure

MDMA: Cerebral edema

• Profuse sweating (pharmacology + activity)

• Loss of electrolytes hemodilution

• Increased vasopressin (ADH)

• Excessive water can lead to passage of water from blood to brain

• Water intoxication

• May result in seizure

MDMA: Hyperthermia

• Elevation of body temperature initiates:

• Rhabdomyolysis• Destruction of skeletal muscle cells• Renal damage from toxic contents of cells

• Disseminated intravascular coagulation• Diffuse activation of clotting cascade• Depletion of clotting factors bleeding

• Multi-organ failure

MDMA-Induced Hyperthermia

Ambient temperature

Physical exertion

Drug action

Example

• Alleged ingestion of 42 tablets of MDMA by a male in his home• Plasma MDMA concentration 0.77 mg/100 mL• No significant symptomatology

• 18 year old male, admitted to hospital unconscious and convulsing after ingestion of 3 tablets of MDMA• MDMA concentration 0.13 mg/100 mL• Died in hospital

MDMA Deaths in Ontario(1999-2002)

• MDMA intoxication was cited as the cause of death in 12 fatalities between 1999 and 2002

• Two suicidal ingestions of MDMA

• 10 accidental MDMA overdoses

Case Report: Death due to MDMA

• 16 year old teenager found collapsed outside a Toronto night club in July 2001

• Admitted to hospital in critical condition:• Hyperthermia, “clothes soaking wet”• “Persistant tachycardia”• “Profound coagulopathy”• Rhabdomyolysis

• Died approximately 9 hours after admission

• Pharmacological resemblance to MDMA• Has been misrepresented as “Ecstasy” • More potent than MDMA or MDA• Increased hallucinogenic effects• Toxicity similar to MDMA but +++

• Agitation, restlessness• Tachycardia• Convulsions• Hyperthermia

Other “ecstasy” deaths:Paramethoxyamphetamine

PMA: Example Cases

• Three deaths due to PMA overdose in Ontario

• 2 men, 1 woman – 18-19 years of age

• All presumed they were taking ‘Ecstasy’

• Seizures, hyperthermia (42.9oC), agitation

• PMA detected at fatal blood concentrations

• MDMA and MDA not detected in any case

Martin, 2001. J. Analytical Tox. Vol. 25: 649-651.

Case example: MDMA and driving

• 21 year old male, driving home from all-night club

• Pulls behind police officer on general patrol

• Honks loudly and indicates for officer to stop

• Indicates he and his passenger are “being followed by 10 cars who are ‘out to get them’”

• Also implicates a parked mini-van and customers in a nearby restaurant as people who are following and “looking at them”

Case example: MDMA and driving

• Observations of the police officer:

• Very excited, nervous manner

• Wide-eyed

• Jerking movements

• Constantly turning and surveying environment

• Walking aimlessly, erratically

• Constantly fidgeting

• Eyes blood shot, lips chapped and bleeding

Case example: MDMA and driving

• Both driver and passenger admit to taking 1 tablet each of “Ecstasy”

• MDMA can cause paranoia, anxiety and hallucinations

• MDMA has also been shown to impair coordination, ability to maintain attention, and may cause increases in risk taking behaviour

KetamineVitamin K, Super Acid, Special K,

K, Horse tranquilizer, Kit kat,

Ketamine

• Human and Veterinary Anesthetic• Ketalar®, Ketaject®, Vetalar®, Ketaset®

• Chemically related to PCP (“Angel dust”)

• Rapid acting, Short acting

• Sedative, Amnesic, Analgesic

• Profound dissociative anaesthesia• Trance-like state

• Separation of perception from sensation

Ketamine: Pharmacology

• Administer by injection, insufflation, smoking

• Onset of effects within 5-10 minutes

• Oral ingestion subject to first-pass effect

• Onset of effects within approx 30-45 minutes

• Amnesia occurring within 15 minutes

• Brief duration of effects (approx 30 minutes)

• t½ is 3-4 hours

• Active metabolite norketamine

Ketamine: Desired effects

• Auditory, visual, sensory hallucinations

• Enhanced insight into existence

• Goal is not to induce full anesthesia

• Emergence effects• Vivid dreams•“Out of body” experiences• Floating sensations• Hallucinations

Ketamine: Desired effects

“I run my hands over my body and both my hands and my body parts feel weird, and disconnected – they do not feel like me…it strikes me as very interesting. I realize that I have to really focus on the existence of my body and my physical state in order to be aware of them…I feel like I am on another plane.”

www.erowid.org/experiences

Ketamine: Desired effects

“The trip started amazing. I crawled to the mirror, not being able to walk, looked in and jumped through to see my other side. I thought I had entered the mirror and was staring back at me…I looked down at my dog and to my surprise he was frozen in time. I tried to pet him and I hit a sheet of glass. This is when I realized I was still ‘in the mirror’.”

www.erowid.org/experiences

Ketamine: Unpleasant effects

• Dizziness

• Nausea & Vomiting

• Incoordination

• Immobility

• Anxiety & Agitation

Ketamine Toxicity

• Seizure

• Hypertension

• Tachycardia

• Cardiac arrythmia

• Loss of consciousness

• Respiratory depression

• Depressant properties are when combined with other central nervous system depressants

Case example: Sudden death due to ketamine injection

• 26 year old man, respiratory technician

• Found dead in his home

• Tourniquet on left arm

• One syringe under the body

• Second syringe in right hand

• 2 vials of Ketalar® found at scene

Case example: Sudden death due to ketamine injection

• Ketamine: 0.69 mg/100 mL in heart blood

• Trace amounts of alcohol in blood

• No other drugs detected

• Cause and manner of death determined to be accidental ketamine intoxication

GHBGamma hydroxybutyrate

Liquid Ecstasy, Liquid X, Scoop, Georgia Home Boy, “G”, Grievous Bodily Harm, “Easy Lay”

Gamma Hydroxybutyrate (GHB)

• CNS depressant and hypnotic

• Easily synthesized, numerous recipes internet

• Salty taste “like old sea water”

• Availability:

• 2% of Toronto students report using GHB in 2000

• Xyrem® now available by prescription in the U.S. for the treatment of narcolepsy (sodium oxybate)

GHB: Appearance

• Clear, colourless liquid• Slightly thicker than water• May be dyed blue• Transported in:

• Water bottles• Visine bottles • Cough syrup bottles• Water guns

• Also produced in white powder form

GHB: Pharmacology

• Rapid onset (15 - 30 minutes)

• Rapid removal – t½ is 0.5-1 hour

• Duration of effects – dose dependent ( 4

hours)

• Effects – similar to alcohol intoxication

GHB: Desired effects

• Mild alcohol-type intoxication

• Pleasant feeling, sense of well-being

• Reduction of social inhibitions

• Sedation (relaxation and calming)

These effects will be amplified if other central nervous system depressants are co-ingested

GHB: Dose and Response

Low Dose 0.5 – 1.5 gramsSimilar to mild alcohol

intoxication

Medium Dose

1.0 – 2.5 gramsIncreased intoxication, grogginess, slurring of speech, incoherency

High Dose 2.5+ gramsIncreasing sedation, drowsiness and sleep

GHB: Unpleasant Effects

• Excessive sleepiness

• Slurred speech

• Nausea

• Vomiting

• Incontinence

GHB: Toxicity

• Believed by many users to be non-lethal• “Safer and more beneficial than water”• Natural health product as opposed to a drug

• Fatalities due to GHB do occur

• Severe toxicity:• Bradycardia• Hypotension• Coma• Severe respiratory depression and apnea

Case Example: Mixed Drug Intoxication with GHB

• 21 year old male, described by witnesses as “severely” intoxicated on night of his death, loss of bladder control, fecal incontinence, “passed out”

• GHB (33 mg/dL) + EtOH (103 mg/dL)

• MDMA (0.02 mg/dL) + MDA (0.02 mg/dL)

• Cause of death: Mixed drug intoxication

• Manner of death: Homicide

GHB Deaths: Scientific Literature

• Deaths attributed solely to GHB are rare, but have been reported:

• e.g. Kalasinsky et al. J. Forensic Sci. (2001)

• Death of a 22 year old woman following her first ingestion of liquid GHB; death occurred approximately 7 hours after ingestion

• Blood GHB concentration: 65 mg/dL

GHB: Analytical Issues

• Targeted analysis not detected by general screens

• Rapidly removed from the body• End products of metabolism are H2O and CO2

• Virtually undetectable in urine after only 12 h

• GHB is present naturally in the body• Metabolite of gamma-aminobutyric acid (GABA)

• Elevated in postmortem cases

Gamma butyrolactone (GBL)

• Readily available industrial chemical

• No pharmacological activity

• Precursor to GHB in illicit manufacture

• Converted to GHB in the body

• Faster onset of action than GHB

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1,4 Butanediol (1,4 BD)

• Industrial compound

• Not used in the illicit manufacture of GHB

• Converted to GHB in the body• 1, 4 BD -OH-butyraldehyde GHB• Alcohol dehydrogenase, aldehyde dehydrogenase

• Effects same as GHB

• Slower onset of action

Drug facilitated sexual assault

Drug facilitated sexual assault

• An old crime (Mickey Finn)

• Victim incapacitated by drug(s)

• Sexual predator spikes drink

• Voluntary intoxication

• Wide range of substances encountered

Typical Scenario

• Victim - one or more alcoholic drinks

• Drink left unattended

• Victim loses track of events

• Wakes in a strange place

• May be inappropriately dressed

• Inability to recall events

Reported symptoms

• Reduced inhibition• Impaired judgment• Confusion • Dizziness• Drowsiness• Impaired memory• Loss of consciousness• Nausea

Date rape drugs

Any drug which alters social inhibitions, decreases the level of consciousness and/or

causes amnesia or confusion in an individual, thereby enabling an assailant to control or

overpower the individual.

Drugs encountered

• Alcohol• Benzodiazepines• Gamma-hydroxybutyrate• Hallucinogens• Ketamine• Opiates• Chloral hydrate• Muscle relaxants

Alcohol

• Most frequently encountered

• Victims may voluntarily consume

• Rapidly absorbed into blood

• Onset of effects dependent on tolerance

• Degree of effects dependent on tolerance

• Elimination from the blood is rapid

Alcohol: Effects

• Central nervous system depressant

• Increased sociability

• Decreased inhibitions

• Impairment of mental and motor functions

• Sedation and loss of consciousness

• Will increase the effects of other sedatives!

Benzodiazepines (“Benzos”)

• Flunitrazepam (Rohypnol) – media hype

• Any benzodiazepine may be used in DFSA

• Most frequently prescribed sedative drugs

• Rx: insomnia, anxiety, seizures

• Readily available

• Fast-acting

Benzodiazepines

• Flunitrazepam - (Rohypnol)• Lorazepam - (Ativan )• Alprazolam - (Xanax )• Diazepam - (Valium )• Triazolam - (Halcion )• Clonazepam - (Clonapam )• Flurazepam - (Dalmane )• Chlordiazepoxide - (Librium )

Lorazepam

• Prescription drug - Ativan• Rx: Insomnia, Anxiety• Onset of action within 30-40 minutes• Effects last up to 8 hours• Confusion• Sedation• Amnesia• Half-life is 10-20 hours

Flunitrazepam

Rohypnol®, Roofies, Roches, Rubies, R-2s

Flunitrazepam

• Not marketed in U.S. or Canada

• Available in Europe, Mexico, Central America

• Heroin users – enhance effects, self-medicate

• Reformulated in countries where it is prescribed• Clear beverages blue colour• Coloured beverages cloudy appearance

• 2 mg tablets restricted to inpatients only

Flunitrazepam: Effects

• High potency (10x that of diazepam (Valium®))

• Onset of effects is 20-30 minutes

• Rapid loss of consciousness and muscle relaxation

• Amnesia occurring within 30 minutes

• Confusion, sedation, slurring of speech

• Peak sedation after 1-2 hours lasting up to 12 h

• Half-life is 10-25 hours

Diphenhydramine

Diphenhydramine

• Readily available

• Primary effect of the drug is antihistamine

• Anti-nauseant (as Gravol®)

• “Older” antihistamine: causes sedation

• In combination with ethanol: sedation

Is GHB the date rape drug?

GHB: Example Case

• 48 year old woman met internet date at her home• Accused mixed a “relaxing health product” with a

sports drink and gave to the complainant• Complainant experienced unconsciousness for

approximately 4 hours• Physical perception of being assaulted• Urine samples collected within 12 hours after the

assault were positive for GHB

Stillwell, 2002. J. Forensic Sci. Vol. 47, No. 5

GHB and DFSA

• Odourless, colourless, easily dissolves

• Simple and inexpensive to manufacture

• Rapid onset of effects

• Causes unconsciousness

• Causes amnesia – real or perceived?

• Becomes rapidly undetectable in the body

The DFSA Investigation

Role of Toxicology

• Laboratory analysis

• Interpretation of findings

• Case consultation

• Letters of opinion

• Provision of viva voce evidence

• Scientific research

• Education

Role of Toxicology

• Analysis can be performed on both biological and non-biological samples

• Non-biological evidence includes: cups and glasses, food, tablets, liquids, powders, vomit, stains from spilled drinks…

• Sexual assault kits are supplied by CFS have containers for blood and urine collection

Biological submissions

Otherwise…

• Blood collected within 48 hours of the offence

• Urine collected within 72 hours of the offence

• Collected in CFS sexual assault kit

Best case scenario is blood and urine collected within 24 hours of the offense.

Case history information

• Date and time of drugging

• Date and time of assault

• Date and time of awakening

• Location of crime

• Evidence recovered from the scene

Crime and scene information

Case history information

• Age and sex

• Alcohol and recreational drugs used

• Medications recently ingested

• Symptoms reported by victim

• Witnesses description of symptoms

• Types of specimens collected from victim

Victim information

Case history information

• Age and sex

• Alcohol and drug history

• Medications readily available to suspect

• Occupation and hobbies• Ketamine Veterinary tranquilizer• GHB Used by body-builders

Suspect information

DFSA: Example Case

Case History

The complainant, a 15 year old girl, reported feeling “woozy” and “out of it” after drinking chocolate milk with her step-father. She was aware of the accused sexually assaulting her but was unable to resist.

The complainant’s mother was home at the time of the assault, but was napping upstairs.

The Investigation

• Mother of complainant phoned police

• Complainant taken to hospital

• Sexual assault kit performed

• Two empty cartons of chocolate milk recovered from scene