4.5 Article

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

Journal

EUROPEAN NEUROPSYCHOPHARMACOLOGY
Volume 25, Issue 10, Pages 1637-1649

Publisher

ELSEVIER SCIENCE BV
DOI: 10.1016/j.euroneuro.2015.05.007

Keywords

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

Funding

  1. Instituto de Salud Carlos III (ISC-III) [FIS 98/0181, 01/1336]
  2. Ministerio de Educacion y Ciencia (MICINN) [FI09/00355]
  3. Generalitat de Catalunya [2009SGR718]

Ask authors/readers for more resources

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 100 mg doses of MDMA separated by 4 h. 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% C-max and +17.1% AUC for MDMA and + 14.2% C-max and +10.3% AUC for MDA) and HMMA and HMA concentrations lower ( 43.3% C-max and -39.9% AUC for HMMA and -33.2% C-max 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 4 h interval there exists a phenomenon of acute tolerance to its effects. (C) 2015 Elsevier B.V. and ECNP. All rights reserved.

Authors

I am an author on this paper
Click your name to claim this paper and add it to your profile.

Reviews

Primary Rating

4.5
Not enough ratings

Secondary Ratings

Novelty
-
Significance
-
Scientific rigor
-
Rate this paper

Recommended

No Data Available
No Data Available