Human pharmacology of 3,4-methylenedioxymethamphetamine (MDMA, ecstasy) after repeated doses taken 4h apart Human pharmacology of MDMA after repeated doses taken 4h apart

Magí Farré, Angels Tomillero, Clara Pérez-Mañá, Samanta Yubero, Esther Papaseit, Pere Nolasc Roset, Mitona Pujadas, Marta Torrens, Jordi Camí, Rafael de la Torre

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15 Citations (Scopus)

Abstract

© 2015 Elsevier B.V. and ECNP. 3,4-Methylenedioxymethamphetamine (MDMA, ecstasy) is a popular psychostimulant, frequently associated with multiple administrations over a short period of time. Repeated administration of MDMA in experimental settings induces tolerance and metabolic inhibition. The aim is to determine the acute pharmacological effects and pharmacokinetics resulting from two consecutive 100mg doses of MDMA separated by 4h. Ten male volunteers participated in a randomized, double-blind, crossover, placebo-controlled trial. The four conditions were placebo plus placebo, placebo plus MDMA, MDMA plus placebo, and MDMA plus MDMA. Outcome variables included pharmacological effects and pharmacokinetic parameters. After a second dose of MDMA, most effects were similar to those after a single dose, despite a doubling of MDMA concentrations (except for systolic blood pressure and reaction time). After repeated MDMA administration, a 2-fold increase was observed in MDMA plasma concentrations. For a simple dose accumulation MDMA and MDA concentrations were higher (+23.1% Cmax and +17.1% AUC for MDMA and +14.2% Cmax and +10.3% AUC for MDA) and HMMA and HMA concentrations lower (-43.3% Cmax and -39.9% AUC for HMMA and -33.2% Cmax and -35.1% AUC for HMA) than expected, probably related to MDMA metabolic autoinhibition. Although MDMA concentrations doubled after the second dose, most pharmacological effects were similar or slightly higher in comparison to the single administration, except for systolic blood pressure and reaction time which were greater than predicted. The pharmacokinetic-effects relationship suggests that when MDMA is administered at a 4h interval there exists a phenomenon of acute tolerance to its effects.
Original languageEnglish
Pages (from-to)1637-1649
JournalEuropean Neuropsychopharmacology
Volume25
Issue number10
DOIs
Publication statusPublished - 1 Oct 2015

Keywords

  • CYP2D6
  • Ecstasy
  • MDMA
  • Pharmacokinetics
  • Pharmacologic effects
  • Repeated dose

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