Overview of MDMA-related Literature for March 2002
One human clinical trial (Pichini et al. 2002), two studies comparing ecstasy users with non-users (Reneman et al. 2002a; Reneman et al. 2002b), two reports of ecstasy user demographics (Arria et al. 2002; Von Sydow et al. 2002), one report examining other ecstasy-related topics (Bateman 2002), two reviews (Kish 2002; Parrott 2002), and four in vitro or non-human animal studies (Hansen et al. 2002; Hatzidimitriou 2002; Matuszewich et al. 2002; Reneman et al. 2002a) were located during this interval.
Human Pharmacology: Saliva
MDMA was detected in saliva up to 10 h after a 100 mg dose in a study in male volunteers, with detection made via GC-MS and with an experimental immunochromatographic assay (Pichini et al. 2002). MDMA was the only compound detectable in saliva, with other metabolites (MDA, HMMA) either absent or detectable at trace levels only.
Imaging Studies
A study performed by Reneman and colleagues, current ecstasy users had decreased, 5HT2A receptor site density when compared with controls, as estimated by imaging with the radioligand [123-I]R91150. Abstinent ecstasy users, on the other hand, had greater [123-I]R91150 binding ratios (Reneman et al. 2002a, Study 1). Study findings indicate that changes in 5HT2A receptor density might be dependent on time since last use of ecstasy. An MRS imaging study conducted by the same team (Reneman et al. 2002b) found that ecstasy users had reduced levels of N-acetylaspartate, considered a marker of neuronal function, in mid-frontal gray matter when compared with controls, but not in occipital or parietal cortex. The reported reduction in NA in ecstasy users stands in contrast to previously reported findings that ecstasy users and non-users did not differ in levels of NA (Chang et al. 1999), perhaps because participants in the study conducted by Reneman et al. used six times as much ecstasy. However, since both studies employed relatively small samples, differences may reflect variance found in the general population.
Ecstasy User Demographics
Ecstasy use in dance event attendees was examined in a brief report (Arria et al. 2002). A study examining drug use in a large representative sample of German adolescents and young adults (Von Sydow et al. 2002) also reported on rates of abuse and dependence in this population and noted cohort effects. A general decline in ecstasy use was found over time in this sample in both age cohorts and in both genders, with rates of diagnosed dependence and abuse also declining over time, possibly as a result of Òloss of magicÓ over time.
Ecstasy and Health Care, Reviews
An examination of poisons database subscription and use, mostly by accident and emergency care personnel, found that ecstasy was the seventh most frequently accessed topic [Bateman 2002, abstract only]. One of two reviews located offered a critique of imaging studies (Kish 2002), describing serious flaws in some imaging studies and offering alternative explanations for study results.
Monkeys: Neuroendocrine Study
In a study in squirrel monkeys, there was a trend toward lower prolactin response to the serotonergic drug mCPP 2 weeks after a probably neurotoxic MDMA regimen , and prolactin response was significantly enhanced 3.5 years after MDMA administration in squirrel monkeys, a finding indicative of altered (possibly compensatory) serotonin function after administration of probably neurotoxic doses of MDMA (Hatzidimitriou et al. 2002). Since similar findings were reported in squirrel monkeys given d-fenfluramine, it would appear that the two compounds similarly affect prolactin response to mCPP.
Rats: Stress and Neurotoxicity
When exposed to immobilization stress, rats given a demonstrably neurotoxic dose of MDMA in a study conducted by Matuszewich and colleagues (Matuszewich et al. 2002). Yet unlike saline-treated rats, MDMA-treated rats did not show an increase in pre-frontal dopamine after stress, suggesting that MDMA neurotoxicity selectively alters some aspects of stress response while leaving others intact. In a companion study of 5HT2A receptor density in rats intended to be compared with a study in humans (Reneman et al. 2002a, Study 2), rats given a neurotoxic regimen of MDMA were found to have decreased 5HT2A receptors (measured via [123-I]R91150 radioligand binding) 3 days after drug administration and an increase in receptors 30 days post-drug, and 5-HT and 5-HIAA were found to be reduced below control levels in rats killed 3 and 30 days after MDMA administration. These findings either lend support to the hypothesized increase in 5HT2A receptor density resulting from reduced serotonergic function, or to effects being related to time since last ecstasy use in humans. Vesicular transport of dopamine was studied in synaptosomes taken from rats given MDMA in a cool or room temperature environment (Hansen et al. 2002). Findings supporting a role for protein kinase C in MDMA-induced reduction in dopamine transport are described, and comparisons between these results and studies using methamphetamine suggest that methamphetamine has far greater effects on vascular transport of DA than MDMA, as a single dose of 15 mg/kg methamphetamine produced effects similar to those seen after repeated doses of 10 mg/kg MDMA.