During March 2003, one human clinical trial, one study in ecstasy users, 2 other studies in humans (a post-mortem study, a study of blood samples, a study of street ecstasy), 2 case reports, 3 in vitro and non-human animal studies, and one forensic study (not summarized) were found.

Enantiomers of MDMA and its Metabolites Detected

Researchers described a method for detecting MDMA enantiomers (different forms), and MDMA metabolites HMMA and MDA (Pizarro et al. 2003). They used samples of blood and urine drawn from one male volunteer (selected from a previous study) given 100 mg MDMA. Study findings indicate that more than one enzyme or process is involved in MDMA metabolism, since the deposition of the metabolite HMMA is not stereoselective (one form more readily metabolized than another), whereas MDMA deposition is stereoselective.

Changes in Serotonin Transporter: Gone in a Year or Two?

In the second study using the radioactive compound (radioligand) [11-C]-(+)-McN5652, researchers in Germany estimated serotonin transporter sites in the brains of 30 current ecstasy users, 29 abstinent ecstasy users, 29 polydrug users and 29 non-drug user controls (Buchert et al. 2003). Current ecstasy users had slightly lower (no more than 6% lower than controls) ligand binding ratios (estimating serotonin transporter sites) in mesencephalon, caudate and thalamus than polydrug user or non-drug user controls, but former users (abstinent for an average of 514 days) did not have lower ligand binding ratios. These findings suggest that changes in the serotonin system after regular, heavy ecstasy use are reversible.

Case Reports

Case reports located this month include a case of urinary retention after use of an unspecified amount of ecstasy in a 17-year old boy (Inman et al. 2003) and a case series of fatalities occurring after the coadministration of the MAO inhibitor moclobemide (Vuori et al. 2003). All deaths reported occurred in Western Finland, two in proximity to each other, suggesting that people may have been acting in response to a rumor or misguided advice on the use of psychiatric drugs in combination with ecstasy to enhance drug effects or as protection against possible neurotoxicity.

MDMA distribution in the Brain: A Post-Mortem Study

A post-mortem investigation used an immunoassays and signal amplification techniques to detect MDMA and MDA in the brains of two ecstasy-related fatalities (MDMA detectable in blood on autopsy), with comparisons made in brains from age-matched controls (De Letter et al. 2003). MDMA was detectable in all four cortical lobes of the ecstasy-related fatalities, and in lentiform nucleus, cerebellar vermis, mammillary bodies, hypothalamus and hippocampus. Staining indicated MDMA in some pituitary cells, findings the authors interpret as associated with acute neuroendocrine effects of MDMA (for example, see Grob et al. 1996; Vollenweider et al. 1998; Harris et al. 2002). Overall, study findings indicate that MDMA is taken up and widely distributed throughout the brain, though changes in distribution occurring after death cannot be ruled out.

No Ecstasy in Blood from Plasma Donors, Street Ecstasy in Denmark.

A study failed to detect MDMA, MDA or MDE in blood from regular (possibly paid) plasma donors in the US and Germany (Peters et al. 2003), though cocaine and cannabis were detected in some cases, particularly those from the US. A study of street ecstasy contents assessed from seized drugs in Denmark found that 24 of 39 samples (62%) contained MDMA, with dosage varying from 15 to 145 mg (Simonsen et al. 2003).

MDMA Alters Subsequent Drug Effects in Mice and Rats

A study in mice found that demonstrably neurotoxic and non-neurotoxic MDMA dose regimens made the animals even more active when given a subsequent dose of MDMA, or repeated doses of cocaine, 5 days later (Itzhak et al. 2003). However, only the mice given a neurotoxic dose regimen continued to show behavioral sensitization when MDMA was given 35, 50 and 80 days later. A study in rats found that a presumably neurotoxic regimen of MDMA did not affect conditioned place preference (indirect measure of drug reward), for cocaine, heroin or MDMA (Cole et al. 2003), and reduced conditioned place preference for ethanol (alcohol). Both studies suggest that MDMA consumption may alter how other drugs are experienced.

Estrogen and MDMA in Rats

A study in ovarectomized female rats found that animals given an estrogen implant had higher rates of locomotion after receiving S-(+)-MDMA (Zhou et al. 2003). These findings suggest that estrogen may modulate at least some acute effects of MDMA. However, it is notable that the authors used S-(+)-MDMA rather than the racemate (a mixture of R-(-) and S-(+)-MDMA). Recent findings in mice (Fantegrossi et al. 2003) as well as human studies with the related compound MDE (Spitzer et al. 2001) suggest that differences in effects of the enantiomers and the racemate are great enough to preclude generalizing from findings based on administering one enantiomer.