Pharmacokinetic profile of single and repeated oral doses of MDMA in squirrel monkeys: relationship to lasting effects on brain serotonin neurons.
Annis O. Mechan, Jie Yuan, George Hatzidimitriou, Rodney J. Irvine, Una D. Mccann, George A. Ricaurte
Neuropsychopharmacology February 2006 DOI: 10.1038/sj.npp.1300808 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Experimental study Peer reviewed |
|---|---|
| Population | Squirrel monkeys |
| Intervention | MDMA |
| Duration | 2 weeks follow-up |
| Topics | MDMA Serotonin |
| Key findings | Oral MDMA in squirrel monkeys produced plasma profiles similar to humans, and plasma MDMA concentrations correlated with regional brain serotonin deficits seen two weeks later. The authors suggest that these neurotoxic levels overlap with those in some recreational ecstasy users and are two to three times higher than those from a controlled 100-150 mg human dose. |
Abstract
A large body of data indicates that (+/-)3,4-methylenedioxymethamphetamine (MDMA, 'ecstasy') can damage brain serotonin neurons in animals. However, the relevance of these preclinical data to humans is uncertain, because doses and routes of administration used in animals have generally differed from those used by humans. Here, we examined the pharmacokinetic profile of MDMA in squirrel monkeys after different routes of administration, and explored the relationship between acute plasma MDMA concentrations after repeated oral dosing and subsequent brain serotonin deficits. Oral MDMA administration engendered a plasma profile of MDMA in squirrel monkeys resembling that seen in humans, although the half-life of MDMA in monkeys is shorter (3 vs 6-9 h). MDMA was biotransformed into MDA, and the plasma ratio of MDA to MDMA was 3-5 / 100, similar to that in humans. MDMA accumulation in squirrel monkeys was nonlinear, and plasma levels were highly correlated with regional brain serotonin deficits observed 2 weeks later. The present results indicate that plasma concentrations of MDMA shown here to produce lasting serotonergic deficits in squirrel monkeys overlap those reported by other laboratories in some recreational 'ecstasy' consumers, and are two to three times higher than those found in humans administered a single 100-150 mg dose of MDMA in a controlled setting. Additional studies are needed on the relative sensitivity of brain serotonin neurons to MDMA toxicity in humans and non-human primates, the pharmacokinetic parameter(s) of MDMA most closely linked to the neurotoxic process, and metabolites other than MDA that may play a role.
Comparable studies
Other preclinical and animal studies on MDMA, most cited first.
Citations in the library
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- Neurotoxicity of methylenedioxyamphetamines (MDMA; ecstasy) in humans: how strong is the evidence for persistent brain damage? Addiction February 27, 2006
- MDMA-assisted therapy: A new treatment model for social anxiety in autistic adults. Progress in Neuro-Psychopharmacology and Biological Psychiatry January 4, 2016
- Neuroimaging findings with MDMA/ecstasy: technical aspects, conceptual issues and future prospects Journal of Psychopharmacology March 1, 2006
- Methylenedioxymethamphetamine (MDMA) in Psychiatry Journal of Clinical Psychopharmacology October 10, 2018
- Drug seeking in response to a priming injection of MDMA in rats: relationship to initial sensitivity to self-administered MDMA and dorsal striatal dopamine The International Journal of Neuropsychopharmacology March 25, 2010
and 29 more in the library
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