Repeated doses administration of MDMA in humans: pharmacological effects and pharmacokinetics.
M Farré, Rafael de la Torre, Brian O Mathúna, Pere N. Roset, Ana M. Peiró, Marta Torrens, Jordi Ortuño, Mitona Pujadas, Jordi Camí
Psychopharmacology May 2004 DOI: 10.1007/s00213-004-1789-7 (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 | 9 |
| Population | Healthy male subjects |
| Intervention | MDMA |
| Dose | 100 mg |
| Duration | Two doses separated by 24 hours |
| Topics | MDMA |
| Key findings | A second 100 mg dose of MDMA taken 24 hours after the first led to a disproportionate rise in plasma MDMA concentrations (AUC +77%, Cmax +29%), suggesting metabolic inhibition. Pharmacological effects were slightly higher after the second dose but lower than expected from the concentration increase. |
Abstract
3,4-Methylenedioxymethamphetamine (MDMA, "ecstasy") is increasingly used by young people for its euphoric and empathic effects. MDMA presents non-linear pharmacokinetics, probably by inhibition of cytochrome P450 isoform 2D6. Users are known to often take more than one dose per session. This practice could have serious implications for the toxicity of MDMA. To evaluate the pharmacological effects and pharmacokinetics of MDMA following the administration of two repeated doses of MDMA (24 h apart). A randomised, double-blind, cross-over, placebo controlled trial was conducted in nine healthy male subjects. Variables included physiological, psychomotor performance, subjective effects, endocrine response and pharmacokinetics. MDMA 100 mg or placebo was administered in two successive doses separated by an interval of 24 h. MDMA produced the prototypical effects of the drug. Following a second dose, plasma concentrations of MDMA increased (AUC 77% and Cmax 29%) in comparison with the first. The increase is greater than those expected by simple accumulation and indicates metabolic inhibition. The pharmacological effects after the second dose were slightly higher than those observed after the first in the majority of variables including blood pressure, heart rate, most subjective effects and cortisol concentrations. The effects were similar in the case of pupil diameter, esophoria and prolactin. Pharmacological effects after the second administration were higher than those following the first but lower than expected. A disproportionate increase in plasma concentrations in MDMA and MDA was observed most likely due to metabolic inhibition. This inhibition lasts at least 24 h. Further experiments need to be conducted to evaluate its duration.
Comparable studies
Other randomized controlled trials on MDMA, most cited first.
Citations in the library
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- 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
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Cites 13
- Cardiovascular and neuroendocrine effects and pharmacokinetics of 3, 4-methylenedioxymethamphetamine in humans. Journal of Pharmacology and Experimental Therapeutics July 1, 1999
- Human Pharmacology of 3,4-Methylenedioxymeth-amphetamine ("Ecstasy"): Psychomotor Performance and Subjective Effects Journal of Clinical Psychopharmacology August 1, 2000
- Pharmacology of MDMA in Humans Annals of the New York Academy of Sciences September 1, 2000
- The serotonin uptake inhibitor citalopram reduces acute cardiovascular and vegetative effects of 3, 4-methylenedioxymethamphetamine (‘Ecstasy’) in healthy volunteers Journal of Psychopharmacology May 1, 2000
- Cardiovascular Effects of 3,4-Methylenedioxymethamphetamine: A Double-Blind, Placebo-Controlled Trial Annals of Internal Medicine December 19, 2000
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