Direct comparison of (±) 3,4-methylenedioxymethamphetamine ("ecstasy") disposition and metabolism in squirrel monkeys and humans

Melanie Mueller, Erin A. Kolbrich, Frank T. Peters, Hans H. Maurer, Una D. McCann, Marilyn A. Huestis, George A. Ricaurte

Research output: Contribution to journalArticlepeer-review

18 Scopus citations


The present study compared the disposition and metabolism of the recreational drug (±) 3,4-methylenedioxymethamphetamine (MDMA, "ecstasy") in squirrel monkeys and humans because the squirrel monkey has been extensively studied for MDMA neurotoxicity. A newly developed liquid chromatography-mass spectrometric procedure for simultaneous measurement of MDMA, 3,4-dihydroxymethamphetamine, 4-hydroxy-3-methoxymethamphetamine, and 3,4-methylenedioxyamphetamine was employed. In both humans and squirrel monkeys, a within-subject design permitted testing of different doses in the same subjects. Humans and squirrel monkeys were found to metabolize MDMA in similar, but not identical, pathways and proportions. In particular, amounts of 3,4-dihydroxymethamphetamine (after conjugate cleavage) and 3,4- methylenedioxyamphetamine were similar in the 2 species, but formation of 4-hydroxy-3-methoxymethamphetamine was greater in squirrel monkeys than in humans. Both species demonstrated nonlinear MDMA pharmacokinetics at comparable plasma MDMA concentrations (125-150 ng/mL and above). The elimination half-life of MDMA was considerably shorter in squirrel monkeys than in humans (2-3 versus 6-9 hours). In both species, there was substantial individual variability. These results suggest that the squirrel monkey may be a useful model for predicting outcomes of MDMA exposure in humans, although this will also depend on the degree to which MDMA pharmacodynamics in the squirrel monkey parallels that in humans.

Original languageEnglish (US)
Pages (from-to)367-373
Number of pages7
JournalTherapeutic drug monitoring
Issue number3
StatePublished - Jun 2009


  • MDMA
  • MDMA metabolites
  • Neurotoxicity
  • Nonlinear pharmacokinetics
  • Serotonin
  • Squirrel monkey

ASJC Scopus subject areas

  • Pharmacology
  • Pharmacology (medical)


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