title: Human pharmacology of 3,4-methylenedioxymethamphetamine (MDMA, ecstasy) after repeated doses taken 2 h apart.
abstract: BACKGROUND
  3,4-methylenedioxymethamphetamine (MDMA, ecstasy) is one of the most abused recreational drugs. Its usual pattern of misuse includes repeated doses taken over a short time period that could influence MDMA pharmacology and toxicity.
  
  
  OBJECTIVE
  This study aims to evaluate the pharmacokinetics and pharmacologically induced effects of two MDMA consecutive doses separated by 2 h.
  
  
  METHODS
  A randomized, double-blind, crossover, and placebo-controlled trial included ten male volunteers participating in two experimental sessions. MDMA was administered as a single 100-mg dose or as a repeated dose (50 mg followed by 100 mg, administered at 2 h apart). Outcome variables included pharmacokinetics, physiological, subjective, and psychomotor effects.
  
  
  RESULTS
  Following the repeated doses, plasma concentrations of MDMA were higher than those expected by simple dose accumulation (+16.2 % AUC; +12.8 % C (max)), but those of HMMA and HMA were significantly lower (-29.8 % AUC; -38.2 % C (max)). After the second dose, physiological effects, psychomotor performance, and subjective effects were lower than expected especially for euphoria and stimulation. MDMA-induced increases in diastolic and systolic arterial pressure and body temperature were in the range of those expected following MDMA concentrations.
  
  
  CONCLUSIONS
  MDMA pharmacokinetics and metabolic disposition following two doses separated by 2 h show that the contribution of the first dose to the MDMA-induced mechanism-based metabolic inhibition was already apparent. The concentrations of MDMA after the second dose were slightly higher than expected. The effects on blood pressure and temperature after the second administration were slightly higher than those following the first, but for heart rate and subjective variables these were lower than expected considering the MDMA concentrations achieved, suggesting a possible tolerance phenomenon.
authors.affiliation: Human Pharmacology and Clinical Neurosciences Research Group, Neurosciences Research Programme, IMIM-Hospital del Mar Medical Research Institute, Doctor Aiguader 88, 08003 Barcelona, Spain.
authors.forename: A M
authors.initials: AM
authors.lastname: Peiró
authors.forename: M
authors.initials: M
authors.lastname: Farré
authors.forename: P N
authors.initials: PN
authors.lastname: Roset
authors.forename: M
authors.initials: M
authors.lastname: Carbó
authors.forename: M
authors.initials: M
authors.lastname: Pujadas
authors.forename: M
authors.initials: M
authors.lastname: Torrens
authors.forename: J
authors.initials: J
authors.lastname: Camí
authors.forename: R
authors.initials: R
authors.lastname: de la Torre
mesh_terms: D000328:Adult; D000339:Affect / Q000187:drug effects* / Q000502:physiology; D001794:Blood Pressure / Q000187:drug effects* / Q000502:physiology; D001831:Body Temperature / Q000187:drug effects* / Q000502:physiology; D018592:Cross-Over Studies; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D006339:Heart Rate / Q000187:drug effects* / Q000502:physiology; D006801:Humans; D008297:Male; D018817:N-Methyl-3,4-methylenedioxyamphetamine / Q000008:administration & dosage* / Q000494:pharmacology; D011597:Psychomotor Performance / Q000187:drug effects* / Q000502:physiology; D055815:Young Adult
chemical_list: D018817:N-Methyl-3,4-methylenedioxyamphetamine