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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 9 Typical Ecstasy User • Age 18-25 • M=F • College student • Rave parties • Poly-drug user © Alcohol Medical Scholars Program 2010 10 Typical Pattern of Use • 1 to 4 tabs per use • Weekends • Dancing • Drinking water © Alcohol Medical Scholars Program 2010 11 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 13 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 15 Common Undesired Effects • ↑ BP • Nausea • ↑ HR • Jaw clenching • ↑Temperature • Teeth grinding • Tremor • Hyponatremia © Alcohol Medical Scholars Program 2010 16 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 20 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 21 Effect of MDMA at the Synapse 5-HT MDMA 5-HTR 5-HTT © Alcohol Medical Scholars Program 2010 22 Effect of MDMA on the Synapse 1. MDMA enters presynaptic cell 5-HT MDMA 5-HTR 5-HTT © Alcohol Medical Scholars Program 2010 23 Effect of MDMA on the Synapse 2. Vesicle breakdown 5-HT MDMA 5-HTR 5-HTT © Alcohol Medical Scholars Program 2010 24 Effect of MDMA on the Synapse 3. Reversal of 5-HT transporter 5-HT MDMA 5-HTR 5-HTT © Alcohol Medical Scholars Program 2010 25 Effect of MDMA on the Synapse 4. Inhibits 5-HT breakdown 5-HT MDMA 5-HTR 5-HTT © Alcohol Medical Scholars Program 2010 26 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 27 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 29 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 31 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 32 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 33 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 34 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 35 Heavy use may be linked to Depression, Anxiety, Paranoia © Alcohol Medical Scholars Program 2010 36 Drug Abuse & Drug Dependence © Alcohol Medical Scholars Program 2010 37 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 38 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 39 Mescaline Serotonin (5-HT) MDMA Amphetamine © Alcohol Medical Scholars Program 2010 40 Screening, Brief Intervention, & Referral to Treatment (SBIRT) • Assess • Advise • Agree • Assist • Arrange © Alcohol Medical Scholars Program 2010 41 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 42 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 43 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