Plasma Pharmacokinetics of 3,4-Methylenedioxymethamphetamine After Controlled Oral Administration to Young Adults
Erin A Kolbrich, Robert S. Goodwin, David A. Gorelick, Robert J. Hayes, Elliot A. Stein, Marilyn A. Huestis
Therapeutic Drug Monitoring May 21, 2008 DOI: 10.1097/ftd.0b013e3181684fa0 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Randomized controlled trial Double-blind Peer reviewed |
|---|---|
| Sample size | 17 |
| Population | Young adults (black, white, and Hispanic) of both sexes |
| Intervention | MDMA |
| Dose | 1.0 mg/kg and 1.6 mg/kg |
| Topics | MDMA |
| Keywords | Pharmacokinetics Cmax Placebo Pharmacology Oral administration |
| Citations | 127 |
| Key findings | MDMA exhibits nonlinear pharmacokinetics: the maximum plasma concentration increases disproportionately with dose, while the metabolite HMMA's maximum concentration does not change significantly between low and high doses. |
Abstract
This study examines the plasma pharmacokinetics of 3,4-methylenedioxymethamphetamine (MDMA) and metabolites 4-hydroxy-3-methoxymethamphetamine (HMMA), 3,4-methylenedioxyamphetamine (MDA), and 4-hydroxy-3-methoxyamphetamine (HMA) in young adults for up to 143 hours after drug administration. Seventeen female and male participants (black, white, and Hispanic) received placebo, low (1.0 mg/kg), and high (1.6 mg/kg) oral MDMA doses (comparable to recreational doses) in a double-blind, randomized, balanced, within-subject design while residing on a closed research unit. Doses were separated by 1 week or more. A fully validated two-dimensional gas chromatography/mass spectrometry method simultaneously quantified MDMA, HMMA, MDA, and HMA. Calibration curves were MDA, 1 to 100 ng/mL; HMA, 2.5 to 100 ng/mL; and MDMA and HMMA, 2.5 to 400 ng/mL. Mean +/- standard deviation maximum plasma concentrations (C(max)) of 162.9 +/- 39.8 and 171.9 +/- 79.5 ng/mL were observed for MDMA and HMMA, respectively, after low-dose MDMA. After the high dose, mean MDMA Cmax significantly increased to 291.8 +/- 76.5 ng/mL, whereas mean HMMA C(max) was unchanged at 173.5 +/- 66.3 ng/mL. High intersubject variability in C(max) was observed. Mean MDA C(max) were 8.4 +/- 2.1 (low) and 13.8 +/- 3.8 (high) ng/mL. HMA Cmax were 3.5 +/- 0.4 and 3.9 +/- 0.9 ng/mL after the low and high doses, respectively. AUC infinity displayed similar trends to C(max), demonstrating nonlinear pharmacokinetics. Times of last plasma detection were generally HMA < MDA < MDMA < HMMA. Mean half-lives (t1/2) of MDMA, MDA, and HMMA were approximately 7 to 8 hours, 10.5 to 12.5 hours, and 11.5 to 13.5 hours, respectively. HMA t1/2 showed high variability. Mean MDMA volume of distribution was constant for low and high doses; clearance was significantly higher after the low dose. This study presents MDMA plasma pharmacokinetic data for the first time from blacks and females as well as measurement of HMMA and HMA concentrations after low and high MDMA doses and more frequent and extended plasma sampling than in prior studies.
Comparable studies
Other randomized controlled trials on MDMA, most cited first.
Citations in the library
Cited by 56
- The safety and efficacy of {+/-}3,4-methylenedioxymethamphetamine-assisted psychotherapy in subjects with chronic, treatment-resistant posttraumatic stress disorder: the first randomized controlled pilot study. Journal of Psychopharmacology July 19, 2010
- The effects of psilocybin and MDMA on between-network resting state functional connectivity in healthy volunteers Frontiers in Human Neuroscience May 27, 2014
- Baths Salts, Spice, and Related Designer Drugs: The Science Behind the Headlines Journal of Neuroscience November 12, 2014
- Safety pharmacology of acute MDMA administration in healthy subjects Journal of Psychopharmacology February 21, 2017
- The ugly side of amphetamines: short- and long-term toxicity of 3,4-methylenedioxymethamphetamine (MDMA, ‘Ecstasy’), methamphetamine and d-amphetamine Biological Chemistry January 2, 2011
and 51 more in the library
Cites 21
- Human Pharmacology of MDMA Therapeutic Drug Monitoring March 19, 2004
- Subjective Reports of the Effects of MDMA in a Clinical Setting Journal of Psychoactive Drugs October 1, 1986
- Cardiovascular and neuroendocrine effects and pharmacokinetics of 3, 4-methylenedioxymethamphetamine in humans. Journal of Pharmacology and Experimental Therapeutics July 1, 1999
- Gender differences in the subjective effects of MDMA Psychopharmacology March 5, 2001
- Human Pharmacology of 3,4-Methylenedioxymeth-amphetamine ("Ecstasy"): Psychomotor Performance and Subjective Effects Journal of Clinical Psychopharmacology August 1, 2000
and 16 more in the library