Club Drugs: MDMA, Ketamine and GHB

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Club Drugs MDMA, Ketamine and GHB

• Teri Martin
• teri.martin_at_jus.gov.on.ca
• November 25, 2003

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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

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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

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MDMAMethylenedioxymethamphetamineEcstasy, XTC,
Adam, Hug-drug, X, MM
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MDMA

• Sympathomimetic and hallucinogenic
• Designer derivative of methamphetamine
• Past, legitimate uses
• Appetite suppressant
• Adjunct to psychotherapy

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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.

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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

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MDMA Desired effects

• Euphoria and benevolence
• Feelings of closeness to others
• Talkativeness
• Desire to interact
• Enhanced perception
• Mild hallucinogenic effects

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MDMA Unpleasant effects

• Immediate effects
• palpitations
• sweating
• teeth-grinding
• jaw-clenching

• Delayed effects
• drowsiness
• muscle aches
• irritability

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MDMA Toxicity

• Hepatic toxicity
• Cardiac toxicity
• Cerebral edema
• Hyperthermia

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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

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MDMA Cardiac Toxicity

• Sympathomimetic (? norepinephrine)
• Hypertension
• Tachycardia
• Arrhythmia
• Increased cardiac workload
• Stroke, hemorrhage, heart failure

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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

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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

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MDMA-Induced Hyperthermia
Drug action
Ambient temperature
Physical exertion
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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

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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

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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

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Other ecstasy deathsParamethoxyamphetamine

• 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

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PMA Example Cases
Martin, 2001. J. Analytical Tox. Vol. 25 649-651.

• 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

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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

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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

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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

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KetamineVitamin K, Super Acid, Special K, K,
Horse tranquilizer, Kit kat,
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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

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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

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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

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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 meit 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 themI feel like I
  am on another plane.

www.erowid.org/experiences
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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
  meI 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
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Ketamine Unpleasant effects

• Dizziness
• Nausea Vomiting
• Incoordination
• Immobility
• Anxiety Agitation

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Ketamine Toxicity

• Seizure
• Hypertension
• Tachycardia
• Cardiac arrythmia
• Loss of consciousness
• Respiratory depression
• Depressant properties are ? when combined with
  other central nervous system depressants

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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

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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

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GHBGamma hydroxybutyrate Liquid Ecstasy, Liquid
X, Scoop, Georgia Home Boy, G, Grievous Bodily
Harm, Easy Lay
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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)

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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

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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

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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

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GHB Dose and Response
Low Dose 0.5 1.5 grams Similar to mild alcohol intoxication
Medium Dose 1.0 2.5 grams Increased intoxication, grogginess, slurring of speech, incoherency
High Dose 2.5 grams Increasing sedation, drowsiness and sleep
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GHB Unpleasant Effects

• Excessive sleepiness
• Slurred speech
• Nausea
• Vomiting
• Incontinence

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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

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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

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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

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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

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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

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Drug facilitated sexual assault
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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

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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

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Reported symptoms

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

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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.
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Drugs encountered

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

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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

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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!

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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

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Benzodiazepines

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

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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

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Flunitrazepam

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

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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

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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

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Diphenhydramine
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Diphenhydramine

• Readily available
• Primary effect of the drug is antihistamine
• Anti-nauseant (as Gravol)
• Older antihistamine causes sedation
• In combination with ethanol ? sedation

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Is GHB the date rape drug?
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GHB Example Case
Stillwell, 2002. J. Forensic Sci. Vol. 47, No. 5

• 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

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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

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The DFSA Investigation
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Role of Toxicology

• Laboratory analysis
• Interpretation of findings
• Case consultation
• Letters of opinion
• Provision of viva voce evidence
• Scientific research
• Education

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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

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

• Otherwise
• Blood collected within 48 hours of the offence
• Urine collected within 72 hours of the offence
• Collected in CFS sexual assault kit

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Case history information
Crime and scene information

• Date and time of drugging
• Date and time of assault
• Date and time of awakening
• Location of crime
• Evidence recovered from the scene

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Case history information
Victim 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

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Case history information
Suspect information

• Age and sex
• Alcohol and drug history
• Medications readily available to suspect
• Occupation and hobbies
• Ketamine ? Veterinary tranquilizer
• GHB ? Used by body-builders

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DFSA Example Case
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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 complainants mother
was home at the time of the assault, but was
napping upstairs.
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The Investigation

• Mother of complainant phoned police
• Complainant taken to hospital
• Sexual assault kit performed
• Two empty cartons of chocolate milk recovered
  from scene