During May 2003, two studies in ecstasy users, two reviews, one paper on ecstasy-related fatalities, two in vitro or non-human animal studies, and three forensic studies (not summarized) were found.

Working Memory Unaltered by Ecstasy Use

Moderate and heavy Ecstasy users performed similarly to non-drug users on a test of working memory without there being any significant differences in brain activity during task performance, as assessed via functional MRI (Daumann et al. 2003). There was a trend for heavy users to respond more slowly when performing the most difficult level of the test, and some differences in brain activity were detected under less stringent tests of significance, such as greater activation of right parietal areas. However, none of these differences were significant when using conservative significance levels. Given that all subjects were recruited from among dance event attendees and reported relatively low use of other drugs save cannabis, study findings suggest that reductions in working memory reported in previous publications (for example Gouzoulis-Mayfrank et al. 2000; Verkes et al. 2000) may be at least partially associated the effects of using other drugs.

Signs of Oxidative Stress in Ecstasy Users

An examination of signs of oxidative stress in Ecstasy users, such as blood levels of vitamins C and E, antioxidant enzyme activity, and signs of lipoperoxide, found lower blood levels of vitamins and greater signs of oxidative stress in Ecstasy users than in non-drug users (Zhou et al. 2003). Duration of use and apparent dosage ("MDMA abuse dose") were both associated with signs of oxidative stress. Study limitations include lack of information on subject recruitment, incompletely reported Ecstasy use histories (no information on lifetime consumption or time from last use of Ecstasy to study day), and lack of information on use of other drugs. However, this is the first reported detection of oxidative stress associated with Ecstasy use in humans, suggesting that humans may be subject to the same stresses seen in non-human animals given MDMA.

Reviews

One review addressed MDMA pharmacology, focusing on models of MDMA neurotoxicity (Lyles and Cadet 2003), and another review examined use of "club drugs" (defined as Ecstasy, ketamine and GHB) in gay and bisexual men, focusing on the relationship between drug use and risky sexual behavior (Romanelli et al. 2003).

Ecstasy-Related Fatalities-Underestimated in Previous Report?

A letter disputing the number and characteristics of Ecstasy-related fatalities reported in a previously published letter in the same journal (Schifano et al. 2003) suggests that number of Ecstasy-related fatalities may have been under-reported in the previous publication (Forrest 2003). The author also suggests that errors in data transcription may have led to reporting presence of MDA in the absence of MDMA. However, both this report and a previous report (Schifano et al. 2003) found that a majority of the reported fatalities involved coadministration of other substances along with Ecstasy, including ethanol (alcohol), benzodiazepines, and opiates. The author does not acknowledge that MDA is sometimes sold as Ecstasy, explaining the presence of MDA in the absence of MDMA in some cases.

More on MDMA and Anxiety and Memory in Rats

Findings in studies of MDMA effects on anxiety in rats were presented in two reports by the same research team. One series of studies found that MDMA dose regimens that did and did not reduce brain serotonin both increased social and non-social anxiety, and lowered 5HT1B receptor density (McGregor, Clemens et al. 2003), though only rats that received a high-dose regimen had reduced 5HT2A/C receptor density. These findings indicate that increased anxiety may be related to changes in serotonin receptors, but not to MDMA-induced reductions in serotonin. The second study reported increased social and non-social anxiety and reduced object memory in rats given MDMA at 16 and 28 degrees C. Rats receiving MDMA at 28 degrees C showed even greater reductions in object memory than rats given MDMA at 16 degrees C. Both doses reduced brain serotonin, though MDMA given at 28 degrees C produced greater reductions in hippocampal serotonin). Differences in performance on the "forced swim" test (a behavioral measure used to assess antidepressants) were only found on the third day of testing, and included greater immobility and fewer attempts to escape in both groups of MDMA-treated rats. Findings suggest that hyperthermia is not required to reduce object memory in MDMA-treated rats, though increased body temperature may exacerbate MDMA-associated memory reductions. These are the first reported forced-swim test findings reported, but it is notable that findings in humans suggest a more complex relationship between Ecstasy use and mood disorders (Lieb et al. 2002; Thomasius et al. 2003), with a large survey finding that psychiatric symptoms often predated Ecstasy use (Lieb et al. 2002).