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Transcript
Ecstasy
Harmless Love Drug or
Dangerous Neurotoxin?
Meg Benningfield, MD
Vanderbilt University
© Alcohol Medical Scholars Program 2010
2
This Talk Will Review:
 What ecstasy is
 Who uses it
 How it works
 Course & treatment
© Alcohol Medical Scholars Program 2010
3
Ecstasy = MDMA
3,4-methylenedioxymethamphetamine
E
Love Doves
X or XTC
Hug Drug
Adam
Disco Biscuit
Euphoria
Go
© Alcohol Medical Scholars Program 2010
4
Mescaline
Serotonin (5-HT)
MDMA
Amphetamine
© Alcohol Medical Scholars Program 2010
5
Ecstasy
• MDMA content varies
• May also contain
– Methamphetamine
– Caffeine
– Dextromethorphan
– Ephedrine
– Cocaine
© Alcohol Medical Scholars Program 2010
6
History
1912
1950s
1970s
1980s
1985
1990s
2000s
Synthesized by Merck
Military investigated use
Used in treatment, no data
Fatalities reported
DEA Schedule 1
Sharp ↑ in use
2 clinical trials for anxiety
© Alcohol Medical Scholars Program 2010
7
This Talk Will Review:
 What ecstasy is
 Who uses it
 How it works
 Course & treatment
© Alcohol Medical Scholars Program 2010
8
Epidemiology
• Worldwide: 9 mil annually
• US: 2.1 mil past year
• Adolescents:
• 4.1% have tried
• > 60% “easy to obtain”
© Alcohol Medical Scholars Program 2010
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Typical Ecstasy User
• Age 18-25
• M=F
• College student
• Rave parties
• Poly-drug user
© Alcohol Medical Scholars Program 2010
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Typical Pattern of Use
• 1 to 4 tabs per use
• Weekends
• Dancing
• Drinking water
© Alcohol Medical Scholars Program 2010
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Poly Drug Use
90% use ≥ 1 other drug
• Alcohol
• Amphetamines
• Marijuana
• Cocaine
• Tobacco
• Opioids
• Hallucinogens
• Nitrous Oxide
© Alcohol Medical Scholars Program 2010
12
Ecstasy Use & Risk Taking
• Impulsivity
• Sexual behavior
–↑ number of partners
–↓ condom use
© Alcohol Medical Scholars Program 2010
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This Talk Will Review:
 What ecstasy is
 Who uses it
 How it works
 Course & treatment
© Alcohol Medical Scholars Program 2010
14
Desired Effects
Empathy
Energy
Euphoria
Photo credit: Tomás Munita for The New York Times February 14, 2009
© Alcohol Medical Scholars Program 2010
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Common Undesired Effects
• ↑ BP
• Nausea
• ↑ HR
• Jaw clenching
• ↑Temperature
• Teeth grinding
• Tremor
• Hyponatremia
© Alcohol Medical Scholars Program 2010
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Rare Severe Effects
• Severe hyperthermia
• Rhabdomyolysis
• Disseminated intravascular coagulation
• Multi-organ failure (liver, kidney, etc.)
• Seizure
• Intracranial bleed or cerebral infarction
• Death
© Alcohol Medical Scholars Program 2010
17
Serotonin Syndrome
•
Hyperactivity
• Tachycardia
•
Confusion
• Shivering
•
Agitation
• Myoclonus
•
Hyperreflexia
• Ocular oscillations
•
↑ Temperature
• Tremor
© Alcohol Medical Scholars Program 2010
18
Risk of serious consequences
↑ with ↑ temperature, ↑ activity
© Alcohol Medical Scholars Program 2010
19
MDMA Alters Brain Chemistry
Serotonin (5-HT)
Trends in cognitive sciences 12(1):31-40
© Alcohol Medical Scholars Program 2010
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How Neurons Communicate
Neurotransmitters are:
1
1.Synthesized in cytoplasm
5
6
2.Released from vesicles
3.Bound to post-synaptic receptors
2
4
4.Recycled by transporters
3
5.Broken down by enzymes
6.Bound to pre-synaptic receptors
© Alcohol Medical Scholars Program 2010
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Effect of MDMA at the Synapse
5-HT
MDMA
5-HTR
5-HTT
© Alcohol Medical Scholars Program 2010
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Effect of MDMA on the Synapse
1. MDMA enters presynaptic cell
5-HT
MDMA
5-HTR
5-HTT
© Alcohol Medical Scholars Program 2010
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Effect of MDMA on the Synapse
2. Vesicle breakdown
5-HT
MDMA
5-HTR
5-HTT
© Alcohol Medical Scholars Program 2010
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Effect of MDMA on the Synapse
3. Reversal of 5-HT transporter
5-HT
MDMA
5-HTR
5-HTT
© Alcohol Medical Scholars Program 2010
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Effect of MDMA on the Synapse
4. Inhibits 5-HT breakdown
5-HT
MDMA
5-HTR
5-HTT
© Alcohol Medical Scholars Program 2010
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Effect of MDMA on the Synapse
5. Inhibits new 5-HT synthesis
5-HT
MDMA
5-HTR
5-HTT
x
© Alcohol Medical Scholars Program 2010
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Effect of MDMA on the Synapse
6. Binds 2A receptor
5-HT
MDMA
5-HTR
5-HTT
x
© Alcohol Medical Scholars Program 2010
28
Long Term Toxicity to 5-HT Neurons
Normal
Ricaurte, et al. (1988) JAMA 260:51-55
After MDMA
© Alcohol Medical Scholars Program 2010
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This Talk Will Review:
 What ecstasy is
 Who uses it
 How it works
 Course & treatment
© Alcohol Medical Scholars Program 2010
30
Emergency Room Visits
• 16,000 visits in 2006
• 3x rate in 2001
• 75% ≤ 26 years old
• M=F
• Other drugs
© Alcohol Medical Scholars Program 2010
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Case 1: Acute toxicity
•
•
•
•
•
•
24 year old F
Confused
Agitated
Visual hallucinations
HR: 150, BP: 90/50, R: 36, T: 41.6˚ C
Labs
– LFTs, CPK, creatinine: elevated
© Alcohol Medical Scholars Program 2010
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Management of Acute Toxicity
• Charcoal if <1h since ingestion
• Monitor vital signs
• Labs:
BUN, creatinine, lytes, LFTs, CPK, UDS
• ECG
© Alcohol Medical Scholars Program 2010
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Management of Acute Toxicity
• Hyperthermia: cooling blanket
• Agitation: diazepam (Valium) 5-30 mg
• Hyponatremia: fluid restrict
• Hypertensive crisis: labetolol (40-80 mg iv q10 min)
• Hypotension: fluids
• Admit to ICU
© Alcohol Medical Scholars Program 2010
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Case 1: Treatment
• Intubated to support ventilation
• 2L IV fluids for hypotension
• Icepacks for hyperthermia
• Diazepam for agitation
• Hemodynamically stable after 8 hours
• Extubated at 23 hours
• Severe complications resolved over 7 d
© Alcohol Medical Scholars Program 2010
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Heavy use may be linked to
Depression, Anxiety, Paranoia
© Alcohol Medical Scholars Program 2010
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Drug Abuse &
Drug Dependence
© Alcohol Medical Scholars Program 2010
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Drug Abuse
Presence of ≥ 1 in 12 months
• Inability to fulfill obligations
• Use in physically hazardous situations
• Use despite legal consequences
• Use despite interpersonal problems
Never met criteria for drug dependence
© Alcohol Medical Scholars Program 2010
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Drug Dependence
Presence of ≥ 3 in 12 months
• Use of larger amounts over longer time
• Desire or attempts to cut down
• ↑ time spent to obtain, use, or recover
• Give up other important activities
• Ongoing use despite problems
• Tolerance
• Withdrawal
© Alcohol Medical Scholars Program 2010
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Mescaline
Serotonin (5-HT)
MDMA
Amphetamine
© Alcohol Medical Scholars Program 2010
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Screening, Brief Intervention, &
Referral to Treatment (SBIRT)
• Assess
• Advise
• Agree
• Assist
• Arrange
© Alcohol Medical Scholars Program 2010
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SBIRT is collaborative
Goal = enhance motivation for change
Feedback personalized, tailored to context
Responsibility belongs to patient
Advice about HOW to change
Menu
options for change
Empathy meeting patients where they are
Self-efficacy strength based
© Alcohol Medical Scholars Program 2010
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Case 2: Chronic complications
22 year old M presents to PCP:
• Episodic chest pain, trouble breathing
• Thinks he may be dying
• Not sleeping well
• Stopped going to class
• Missing days at work
© Alcohol Medical Scholars Program 2010
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Case 2, continued
• Ecstasy every weekend x 6 mos
• Now using “nerve pills” daily to cope
• Pills helped, but now needs more
• Spends day in bed
• Wants prescription
© Alcohol Medical Scholars Program 2010
44
Case 2: Treatment
• Benzodiazepine dependence
–Detoxification
–Outpatient follow-up
• Anxiety, depression
–Cognitive behavioral therapy
© Alcohol Medical Scholars Program 2010
45
This Talk Will Review:
 What ecstasy is
 Who uses it
 How it works
 Course & treatment
© Alcohol Medical Scholars Program 2010
46