Neuropharmacology: MDMA

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Lecture 19 from a college level neuropharmacology course taught in the spring 2012 semester by Brian J. Piper, Ph.D. ( at Willamette University. Pharmacokinetics, pharmacodynamics, and epidemiology of MDMA (ecstasy).

Text of Neuropharmacology: MDMA

  • 1. Brian J. Piper, Ph.D.
  • 2. Goals History Epidemiology Acute Effects Pharmacokinetics Pharmacodynamics Toxicology
  • 3. History3,4-methylenedioxymethamphetamine (MDMA, aka ecstasy, X) 1912: Synthesized by German pharmaceutical company Merck by Anton Kollisch (1888-1916) 1950s: U.S. Army conducted animals studies to determine the lethal dose. 1970s: Mental health workers advocated using MDMA with psychotherapy. There are ongoing studies to use MDMA with talk therapy for anxiety related to post-traumatic stress disorder and among terminally ill cancer patients. 1985: Drug Enforcement Agency (DEA) classifies MDMA as Schedule I 2003: Illicit Drug Anti-Proliferation Act: this increase penalties for ecstasy distribution, possession, or place that condone illicit drug use
  • 4. Chemistry Entactogen: touching within (Nichols) MDMA (methylenedioxymethamphetamine)MDA (methylenedioxyamphetamine) Amphetamine
  • 5. Pharmacokinetics: Age Meyer, Piper,& Vancolli (i2008) Annals of the Liver New York Academy of Sciences., 1139, MDMA -----> MDA 151-163.
  • 6. Pharmacokinetics: Individual Differences Following Oral Administration of MDMA Plasma MDMA for each marmoset that received 1 mg/kg. 80 70 60 M D M A (n g /m l) Ng/ml 50 Lexi 40 Eric Zale 30 Autumn 20 10 0 0 20 40 60 Time
  • 7. Epidemiology Predictions Year (1996 2010) Sex Urban versus Rural Age (8th grade 30)
  • 8. Ecstasy = MDMA?
  • 9. What is PMA? paramethoxyamphetamine "Death" "Mitsubishi Double Stack" "Killer" "Red Mitsubishi" cheaper substitute for MDMA slower onset, longer effects, more hallucinogenic incidence of toxic side effects much higher than MDMA (narrow safety margin), e.g. hyperthermia
  • 10. MtF: Epidemiology .
  • 11. MtF: Epidemiology .
  • 12. MtF: Urban versus Rural Year Year
  • 13. Epidemiology Adults: MtF
  • 14. Absence of Sex Differences
  • 15. NHSDUH: New users fluctuate NHSDUH, 2011
  • 16. Wastewater analysis Australia was the world leader for MDMA use Samples collected every 6th day (May- June) in Adelaide (SA) Is it ethical to monitor recreational drugs in: City High Schools Prisons
  • 17. Short-term effects of Ecstasy Psychological Physiological Empathy Increase in heart rate Increased energy Increase in blood pressure Openness Reduced appetite Increased sensitivity to Bruxism: grinding teeth sounds & touch Trismus: jaw clenching
  • 18. Pharmacodynamics MDMA increases neurotransmitters (serotonin, norepinephrine, dopamine) & hormones (cortisol, prolactin, oxytocin)
  • 19. Serotonin Serotonin is 5-hydroxytryptamine (5-HT) The brain uses the amino acid tryptophan (found in bananas, milk, yogurt) to make 5-HT. 5-HT has been implicated in mood (anxiety, depression & aggression), appetite, sexuality, and cognition. ->