Two clinical trials (Forsling et al. 2001; Tancer et al. 2001) were published in this month. Four studies (three imaging studies and one neurocognitive performance study) comparing ecstasy users to non-users appeared (Obergreisser et al. 2001; Reneman et al. 2001a; Reneman et al. 2001b; Zakzanis and Young 2001. Two demographic studies (Siliquini et al. 2001; Boys et al. 2001), one commentary (McCann et al. 2001), one examination of behavior in specific ecstasy users (Mattison et al. 2001), one review of adverse events related to illicit ecstasy use (Kalant 2001), and two studies in non-human animals also appeared.

Human Pharmacology: AVP Release
One of the clinical trials is important because it suggests that the effects of MDMA on water retention (increasing risk of hyponatremia) may be due to one or more MDMA metabolites (Forsling et al. 2001).

Acute Subjective Effects
The other clinical trial found that many of the effects of MDMA did not predictably increased as dose increased, which can be seen as supporting the view that MDMA has complex pharmacology beyond that of classical psychostimulants (Tancer et al. 2001).

MRS Imaging
Two studies of ecstasy users used magnetic resonance spectroscopy to measure concentrations of the neuronal metabolite N-acetylaspartate, which has been used as a marker for neuronal dysfunction. One study, which matched users and non-users according to performance on the test of executive function, did not find a significant difference between users and non-users (Obergreisser et al. 2001). The second study did not match study groups in this manner and reported a relationship between elevated N-acetylaspartate /creatine ratios and decreased neurocognitive performance (Reneman et al. 2001b).

Serotonin Transporters and Memory
Another study conducted by Reneman and colleagues measured verbal recall (via RAVLT) and serotonin transporter (SERT) binding sites (via the radioligand b-CIT) in current and former ecstasy users, and non-user controls (Reneman et al. 2001a). Current, but not former, users had lower b-CIT binding ratios than controls, and both current and former ecstasy users had lower immediate and delayed verbal recall scores compared with controls. However, b-CIT binding ratio was unrelated to verbal recall scores, whereas self-reported cumulative exposure was significantly related to verbal recall scores. There have been ongoing debates about the validity of techniques that attempt to measure serotonin transporter density in living humans (see Kish 2002). This study can be seen as suggesting that putative measures of serotonin transporter density are less sensitive to ecstasy exposure than measures of memory. In a separate publication that seems to use many of the same volunteers, the authors report that differences in b-CIT binding ratios between (what appears to be largely the same groups of) current users and non-users is only statistically significant in female, but not male, users. Yet the report examining verbal memory scores does not examine potential gender differences in verbal performance. Hence it is unclear what relationships both measures (b-CIT binding and performance on tests of verbal memory) have to serotonin function or to gender. A commentary referring to this paper and addressing issues in ecstasy research appeared in the same issue of Archives of General Psychiatry (McCann et al. 2001).

Executive Function
A third study published this month reported that ecstasy users obtained lower scores on a comprehensive measurement of executive function when compared with non-ecstasy users (Zakzanis and Young 2001). Several drug use parameters, including cumulative exposure (number of tablets taken across a lifetime) and frequency of use were related to performance on different tests of executive function. Overall, the literature continues to support an association between illicit ecstasy use and clinically subtle (if not insignificant) decreases in verbal memory and executive function, with little indication of improvement with abstinence from ecstasy.

Demographics and Associations with Unsafe Sex
A study of young men entering the Italian army found that 4.5% of 3274 men surveyed reported having used ecstasy, as compared with 30% reporting use of cannabis (Siliquini et al. 2001). In an investigation of drug use and unsafe sex, 72% of 1169 gay men surveyed at circuit parties reported using ecstasy at least once in the last 12 months, and frequent use of ketamine, poppers and ecstasy were all related to reporting unsafe sex practices (Mattison et al. 2001).

Reasons for Drug Use?
Because findings indicate that users report a number of reasons for their drug use, the study conducted by Boys and colleagues may also be of interest (Boys et al. 2001). Reasons given for ecstasy use were to sustain an activity, to feel good, or to enhance a social activity, with these reasons being very similar to reasons given for using stimulants.

Rats: Immunological Effects
In a study in rats, MDMA reduced production of IgG2a anti-bodies, but not IgM anti-bodies, in female rats, and MDMA also reduced IFN-g, but not IL-6 (Connor et al. 2001). These findings are somewhat similar to those reported in humans, and suggest that MDMA may acutely alter and disrupt immunological function to some degree.

Rabbits: Thermoregulation and Vasoconstriction
Research performed on rabbits suggested that MDMA-induced increases in central body temperature are at least partially due to vasoconstriction that decreases cutaneous blood flow and heat loss (Pedersen and Blessing 2001). MDMA effects on cutaneous blood flow were partially mediated through actions on the sympathetic nervous system, as cervical sympathectomy on one side of the animal attenuated drug-induced blood flow changes on that side. It is not clear how these findings reflect on findings concerning the importance of ambient temperature in causing hyperthermia after the administration of MDMA or ecstasy.