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.
Magí Farré, Angels Tomillero, Clara Pérez‐mañá, Samanta Yubero, Esther Papaseit, Pere-Nolasc Roset, Mitona Pujadas, Marta Torrens, Jordi Camí, Rafael de la Torre
European Neuropsychopharmacology October 2015 DOI: 10.1016/j.euroneuro.2015.05.007 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Randomized, double-blind, crossover, placebo-controlled trial Peer reviewed |
|---|---|
| Sample size | 10 |
| Population | Healthy male volunteers |
| Intervention | MDMA |
| Dose | two consecutive 100 mg doses of MDMA separated by 4 hours |
| Duration | Second dose administered 4 hours after the first |
| Topics | MDMA |
| Keywords | Cyp2d6 Pharmacokinetics Pharmacologic effects Repeated dose |
| Key findings | A second 100 mg MDMA dose given four hours after the first doubled plasma MDMA concentrations but produced mostly similar pharmacological effects, with only systolic blood pressure and reaction time exceeding predictions. MDMA and MDA exposure was modestly higher than expected from simple accumulation, while HMMA and HMA exposure was substantially lower, which the authors attribute to MDMA autoinhibition of its metabolism. The authors argue this indicates acute tolerance to MDMA's effects at a four-hour dosing interval. |
Abstract
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.
Comparable studies
Other randomized controlled trials on MDMA, most cited first.
Citations in the library
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- Use of the CytoSorb adsorption device in MDMA intoxication: a first-in-man application and in vitro study Intensive Care Medicine Experimental June 21, 2020
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