Addiction Biology
June 14, 2013
Sarah Bradbury, Judith Bird, Joyce Colussi‐mas et al.
59 citations
Abstract The current study aimed to elucidate the role of pharmacokinetic ( PK ) parameters and neurotransmitter efflux in explaining variability in (±) 3, 4‐methylenedioxymethamphetamine ( MDMA ) self‐administration in rats. PK profiles of MDMA and its major metabolites were determined after the administration of 1.0 mg/kg MDMA (iv) prior to, and following, the acquisition of MDMA...
The FASEB Journal
April 1, 2013
Jonathan M. Slezak, Melanie Mueller, George A. Ricaurte et al.
MDMA (ecstasy), popularized as a “club drug,” is a psychoactive and abused substance. It is often assumed that the behavioral effects of MDMA are due to central actions, though this has not been tested. Using a quaternary analog of MDMA (qMDMA) we tested that assumption by training male Sprague‐Dawley rats (n = 6) to discriminate intraperitoneal (i.p.) injections of 1.7 mg/kg of MDMA HCl from...
Synapse (New York, N.Y.)
October 2011
Melanie Mueller, Jie Yuan, Concepcion Maldonado Adrian et al.
3,4-Methylenedioxymethamphetamine (MDMA)'s O-demethylenated metabolite, 3,4-dihydroxymethamphetamine (HHMA), has been hypothesized to serve as a precursor for the formation of toxic catechol-thioether metabolites (e.g., 5-N-acetylcystein-S-yl-HHMA) that mediate MDMA neurotoxicity. To further test this hypothesis, HHMA formation was blocked with dextromethorphan (DXM), which competitively...
Psychopharmacology
October 2011
Una D McCann, Robert R Edwards, Michael T Smith et al.
(±)3,4-Methylenedioxymethamphetamine (MDMA) is a popular recreational drug that has potential to damage brain serotonin (5-HT) neurons in humans. Brain 5-HT neurons play a role in pain modulation, yet little is known about long-term effects of MDMA on pain function. Notably, MDMA users have been shown to have altered sleep, a phenomenon that can lead to altered pain modulation. This study...
Neurology
July 4, 2011
Una D. Mccann, Francis P. Sgambati, Alan R. Schwartz et al.
1 citation
Background: Methylenedioxymethamphetamine (MDMA, "ecstasy") is a popular recreational drug of abuse and a selective brain serotonin neurotoxin.Functional consequences of MDMA neurotoxicity have defied ready characterization.Obstructive sleep apnea (OSA) is a common form of sleep-disordered breathing in which brain serotonin dysfunction may play a role.The present study sought to determine...
The Journal of pharmacology and experimental therapeutics
July 2011
Melanie Mueller, Amy K Goodwin, Nancy A Ator et al.
The baboon is potentially an attractive animal for modeling 3,4-methylenedioxymethamphetamine (MDMA) effects in humans. Baboons self-administer MDMA, are susceptible to MDMA neurotoxicity, and are suitable for positron emission tomography, the method most often used to probe for MDMA neurotoxicity in humans. Because pharmacokinetic equivalence is a key feature of a good predictive animal model,...
Synapse
June 3, 2011
Michael W. McLane, Una D. Mccann, George A. Ricaurte
11 citations
A number of published studies have questioned the serotonin neurotoxic potential of 3,4-methylenedioxymethamphetamine (MDMA, "ecstasy") and related drugs (fenfluramine, p-chloroamphetamine) based upon results from Western blot studies using a custom synthesized serotonin transporter (SERT) antibody that found no reduction in the abundance of a 50kDa protein after substituted amphetamine...
Chemical Research in Toxicology
May 10, 2011
Anne Neudörffer, Melanie Mueller, Claire-Marie Martinez et al.
5 citations
The purpose of the present study was to determine if trihydroxymethamphetamine (THMA), a metabolite of methylenedioxymethamphetamine (MDMA, "ecstasy"), or its thioether conjugate, 6-(N-acetylcystein-S-yl)-2,4,5-trihydroxymethamphetamine (6-NAC-THMA), play a role in the lasting effects of MDMA on brain serotonin (5-HT) neurons. To this end, novel high-yield syntheses of THMA and 6-NAC-THMA were...
Drug metabolism and disposition: the biological fate of chemicals
October 2009
Melanie Mueller, Jie Yuan, Anne Felim et al.
The mechanism by which the recreational drug (+/-)-3,4-methylenedioxymethamphetamine (MDMA) destroys brain serotonin (5-HT) axon terminals is not understood. Recent studies have implicated MDMA metabolites, but their precise role remains unclear. To further evaluate the relative importance of metabolites versus the parent compound in neurotoxicity, we explored the relationship between...
Therapeutic Drug Monitoring
June 1, 2009
Melanie Mueller, Erin A Kolbrich, Frank T. Peters et al.
The present study compared the disposition and metabolism of the recreational drug (±) 3,4-methylenedioxymethamphetamine (MDMA, “ecstasy”) in squirrel monkeys and humans because the squirrel monkey has been extensively studied for MDMA neurotoxicity. A newly developed liquid chromatography-mass spectrometric procedure for simultaneous measurement of MDMA, 3,4-dihydroxymethamphetamine,...
Psychopharmacology
October 2008
Una D McCann, Zsolt Szabó, Melin Vranesic et al.
(+/-)3,4-Methylenedioxymethamphetamine (MDMA, "ecstasy") is a recreational drug and brain serotonin (5-HT) neurotoxin. Under certain conditions, MDMA can also damage brain dopamine (DA) neurons, at least in rodents. Human MDMA users have been found to have reduced brain 5-HT transporter (SERT) density and cognitive deficits, although it is not known whether these are related. This study sought...
The Scientific World Journal
2007
Una D. Mccann, George A. Ricaurte
52 citations
Abuse of stimulant drugs invariably leads to a disruption in sleep-wake patterns by virtue of the arousing and sleep-preventing effects of these drugs. Certain stimulants, such as 3,4-methylenedioxymethamphetamine (MDMA), may also have the potential to produce persistent alterations in circadian regulation and sleep because they can be neurotoxic toward brain monoaminergic neurons involved in...
Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology
February 2006
Annis Mechan, Jie Yuan, George Hatzidimitriou et al.
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...
Adicciones
December 15, 2003
Una D. Mccann, George A. Ricaurte
El incremento del consumo de éxtasis (MDMA) por parte de los jóvenes ha obligado al estudio de efectos a corto y medio plazo sobre el SNC. En la última década, se demostró la existencia de neurotoxicidad serotoninérgica en el SNC. Recientemente aparecieron estudios tendentes a demostrar también daño dopaminérgico que se ha evidenciado en experimentación animal. Las diferentes técnicas de...
Science
June 1, 2003
Michael C Mithoefer, Lisa Jerome, Richard Doblin et al.
36 citations
MDMA ("ecstasy") and neurotoxicity.
Science
September 27, 2002
George A. Ricaurte, Jie Yuan, George Hatzidimitriou et al.
179 citations
Retracted
The prevailing view is that the popular recreational drug (±)3,4-methylenedioxymethamphetamine (MDMA, or “ecstasy”) is a selective serotonin neurotoxin in animals and possibly in humans. Nonhuman primates exposed to several sequential doses of MDMA, a regimen modeled after one used by humans, developed severe brain dopaminergic neurotoxicity, in addition to less pronounced serotonergic...
Synapse
September 5, 2002
Liesbeth Reneman, Jan Booij, Jan B. A. Habraken et al.
33 citations
Abstract Recent [ 123 I]β‐CIT single‐photon emission computed tomography (SPECT) studies revealed decreased serotonin transporters (SERT) density in the brain of humans with a history of MDMA (“Ecstasy”) use. However, [ 123 I]β‐CIT SPECT has until now not been validated as a method for detecting such serotonergic lesions. Therefore, the present study was undertaken. Following baseline [ 123...
European Addiction Research
2002
Julio Bobes, Pilar A. Sáiz, María Paz García‐portilla et al.
34 citations
<i>Aim: </i>To measure the prevalence of 3,4-methylenedioxymethamphetamine (MDMA) and other drug use in young males entering compulsory military service in Asturias (northern Spain) and to define trends in MDMA use in this group during the period from 1995 to 1999. We also sought to determine whether MDMA users have distinct personality features or higher levels of sensation seeking....
Neuropsychobiology
2000
George A. Ricaurte, Jie Yuan, Una D. Mccann
291 citations
The popular recreational drug, (±)3,4-methylenedioxymethamphetamine (MDMA; ‘Ecstasy’) is a potent and selective brain serotonin (5-HT) neurotoxin in animals. MDMA-induced 5-HT neurotoxicity can be demonstrated using a variety of neurochemical, neuroanatomical and, more recently, functional measures of 5-HT neurons. Although the neurotoxic effects of MDMA in animals are widely accepted, the...
Neuropsychobiology
2000
Una D. Mccann, Victoria Eligulashvili, George A. Ricaurte
192 citations
(±)3,4-Methylenedioxymethamphetamine (MDMA, ‘Ecstasy’) is a brain serotonergic neurotoxin in experimental animals, including nonhuman primates. It is also an increasingly popular recreational drug of abuse, and doses of MDMA that are used recreationally overlap with those that produce serotonin (5-HT) neurotoxicity in animals. Studies in human MDMA users probing for evidence of brain...
Journal of Neuroscience
June 15, 1999
George Hatzidimitriou, Una D. Mccann, George A. Ricaurte
338 citations
The recreational drug (±)3,4-methylenedioxymethamphetamine (MDMA, “Ecstasy”) is a potent and selective brain serotonin (5-HT) neurotoxin in animals and, possibly, in humans. The purpose of the present study was to determine whether brain 5-HT deficits persist in squirrel monkeys beyond the 18-month period studied previously and to identify factors that influence recovery of injured 5-HT axons....
Neurology
December 1, 1998
Karen I. Bolla, Una D. Mccann, George A. Ricaurte
376 citations
Abstinent MDMA users have impairment in verbal and visual memory. The extent of memory impairment correlates with the degree of MDMA exposure and the reduction in brain 5-HT, as indexed by CSF 5-HIAA.
The Lancet
October 1, 1998
Ud Mccann, Zsolt Szabó, Ursula Scheffel et al.
664 citations
Quantitative PET studies with a ligand selective for 5-HT transporters can be used to assess the status of 5-HT neurons in the living human brain. We show direct evidence of a decrease in a structural component of brain 5-HT neurons in human MDMA users.
Synapse
June 1, 1998
Ursula Scheffel, Zsolt Szabó, William B. Mathews et al.
146 citations
The present study evaluated short- and long-term effects of MDMA (3,4-methylenedioxymethamphetamine) in the baboon brain using PET and [11C](+)McN 5652, a potent 5-HT transporter ligand, as well as [11C]RTI-55, a cocaine derivative which labels both 5-HT and dopamine transporters. Following baseline PET scans with [11C](+)McN5652, [11C](-)McN5652 (the inactive enantiomer of the active...
Drug safety
August 1996
U D McCann, S O Slate, George A. Ricaurte
3,4-Methylenedioxymethamphetamine (MDMA; 'ecstasy') is an increasingly popular recreational drug in the US, Western Europe and Australia. In animals, including nonhuman primates, MDMA is known to damage brain serotonin (5-hydroxytryptamine; 5-HT) neurons. It is not known whether MDMA damages serotonin neurons in the human brain but there is some indication that it may. Although the large...