Single oral doses of (±) 3,4-methylenedioxymethamphetamine (‘Ecstasy’) produce lasting serotonergic deficits in non-human primates: relationship to plasma drug and metabolite concentrations
Melanie Mueller, Jie Yuan, Una D. Mccann, George Hatzidimitriou, George A. Ricaurte
The International Journal of Neuropsychopharmacology May 1, 2013 DOI: 10.1017/s1461145712000582 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Observational animal study Peer reviewed |
|---|---|
| Population | Squirrel monkeys (non-human primates) |
| Intervention | MDMA |
| Dose | 5.7 mg/kg (lowest dose tested; estimated equivalent to 1.6 mg/kg in humans) |
| Topics | MDMA Serotonin |
| Key findings | Single oral doses of MDMA caused lasting, dose-related serotonergic neurochemical deficits in squirrel monkey brains, with even the lowest dose (5.7 mg/kg) producing significant effects in some regions. Serotonergic markers were inversely correlated with plasma MDMA but not with its major metabolites, suggesting the parent compound rather than a metabolite causes serotonin neuron injury. |
Abstract
Abstract: Repeated doses of the popular recreational drug methylenedioxymethamphetamine (MDMA, ‘Ecstasy’) are known to produce neurotoxic effects on brain serotonin (5-HT) neurons but it is widely believed that typical single oral doses of MDMA are free of neurotoxic risk. Experimental and therapeutic trials with MDMA in humans are underway. The mechanisms by which MDMA produces neurotoxic effects are not understood but drug metabolites have been implicated. The aim of the present study was to assess the neurotoxic potential of a range of clinically relevant single oral doses of MDMA in a non-human primate species that metabolizes MDMA in a manner similar to humans, the squirrel monkey. A secondary objective was to explore the relationship between plasma MDMA and metabolite concentrations and lasting serotonergic deficits. Single oral doses of MDMA produced lasting dose-related serotonergic neurochemical deficits in the brains of squirrel monkeys. Notably, even the lowest dose of MDMA tested (5.7 mg/kg, estimated to be equivalent to 1.6 mg/kg in humans) produced significant effects in some brain regions. Plasma levels of MDMA engendered by neurotoxic doses of MDMA were on the order of those found in humans. Serotonergic neurochemical markers were inversely correlated with plasma concentrations of MDMA, but not with those of its major metabolites, 3,4-dihydroxymethamphetamine and 4-hydroxy-3-methoxymethamphetamine. These results suggest that single oral doses of MDMA in the range of those used by humans pose a neurotoxic risk and implicate the parent compound (MDMA), rather than one of its metabolites, in MDMA-induced 5-HT neural injury.
Comparable studies
Other preclinical and animal studies on MDMA, most cited first.
Citations in the library
Cited by 11
- 3,4-methylenedioxymethamphetamine (MDMA): current perspectives Substance Abuse and Rehabilitation November 1, 2013
- Methylenedioxymethamphetamine (MDMA) in Psychiatry Journal of Clinical Psychopharmacology October 10, 2018
- Separating the agony from ecstasy: R(−)-3,4-methylenedioxymethamphetamine has prosocial and therapeutic-like effects without signs of neurotoxicity in mice Neuropharmacology October 6, 2017
- Experimental strategies to discover and develop the next generation of psychedelics and entactogens as medicines Neuropharmacology December 15, 2022
- Subjective and neurocognitive profiling of clinical doses of 3,4-methylenedioxymethamphetamine (MDMA) in healthy volunteers: implications for therapeutic use Molecular Psychiatry April 8, 2026
and 6 more in the library
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