Two case studies, one review of drug interactions in humans, seven in vitro and non-human animal studies, [and a commentary on a study in non-human animals] were found in this time period. Three forensic studies were located; they are not addressed in this update. No human clinical trials or studies of ecstasy users were located.

Case Reports

A case of cervical and mediastinal "air emphysema" (air leak, pneumostadium) was described and reported in a man who reported previous ecstasy use (Badoui et al. 2002). The issue of organ toxicity (specifically in liver) in relation to ecstasy use is addressed through a case series of two hyponatremia-related fatalities whose organs were donated to others and 3 ecstasy users who needed liver transplants (Caballero et al. 2002).

Drugs and Antiretrovirals

Interactions between various psychoactives, including MDMA, and antiretroviral drugs (used to treat AIDS) are discussed in this review by examining case studies, including cases of reported interactions between MDMA and ritanovir (Antoniou and Tseng 2002). The authors encourage doctors to communicate with patients about drug use patterns when prescribing protease inhibitors and other antiretrovirals [paper currently unavailable.]

Cardiac Effects In Rat Right Ventricle

Because MDMA strengthened contractions in rat right ventricle in the presence of the neurotransmitter norepinephrine (NE) and not the beta adrenergic agonist isoprenaline, researchers concluded that MDMA acts as an NE uptake inhibitor, rather than acting on receptors (Cleary et al. 2002). After examining these findings, the authors speculate that human use of MDMA will increase risk of cardiac problems. However, it appears that while they do occur, severe cardiac problems after ecstasy use are relatively rare.

Metabolism of Substituted Amphetamines in Rats

A study comparing metabolism of MDMA with that of MDE in rat brain and plasma found that MDMA is enantioselectively metabolized, with S-(+)-MDMA metabolized more extensively than R-(-)-MDMA (Meyer et al. 2002a). However, they also found finding equal amounts of MDA and HMMA in plasma, but more MDA than HMMA in striatum and cortex, leading the authors to suggest that S-(+)-MDMA is preferentially transported to the brain. MDE was less extensively metabolized than MDMA.

Only Socially Isolated Rats Like Places Associated with MDMA

An investigation into the rewarding affects of amphetamine, MDMA and MDE found that group-housed rats did not prefer a location previously associated with MDMA administration, though they did prefer an amphetamine-associated location (Meyer et al. 2002b). Social isolation increased preference for the MDMA-associated location. Rats in this study found R-(-)-MDMA and S-(+)-MDMA as appealing as the racemate. Even socially isolated rats did not significantly prefer MDE-associated locations, though there was a trend for such preferences. These findings suggest that the rewarding properties of a drug are not solely based in its pharmacology, but are also based the state of an organism, and include factors such as stress (as caused by social isolation).

Anxiety, Serotonin and MDMA Neurotoxicity in Rats

Contradictory findings concerning the long-term effects of neurotoxic and non-neurotoxic doses of MDMA on rat anxiety levels are briefly addressed in this exploration and review (Green and McGregor 2002). Noting that whether MDMA is associated with an increase or a decrease in anxiety may relate to rat strain, the authors propose that neurotoxic doses of MDMA increase anxiety in less anxious strains and decrease anxiety in more anxious strains. However, since even a non-neurotoxic dose of MDMA has been reported to increase anxiety, the authors also suggest that some changes in anxiety appearing after MDMA may be due to changes in neural function rather than neurotoxicity.

Stress Hormones, Sympathetic Activation Enhance MDMA Neurotoxicity

This research investigated the effects of adrenalectomy and inhibition of the sympathetic nervous system on MDMA neurotoxicity in Fischer 344 (F344) rats (Fernandez et al. 2002). Both adrenalectomy and chlorisondamine (peripheral nicotinic receptor antagonist) attenuated MDMA-associated reductions in 5-HT and its metabolite 5-HIAA, but since both treatments also reduced MDMA-induced hyperthermia, their effects may have been mediated through lowering body temperature. However, since chlorisondamine did not fully attenuate MDMA-associated hyperthermia, inhibiting the sympathetic system may reduce MDMA neurotoxicity independent of thermoregulatory or stress-hormone related effects.

Possible Dopamine Neurotoxicity?

When 3 doses of 2 mg/kg MDMA were given every 2 hours were given to squirrel monkeys and baboons, multiple measures detected neurotoxicity to brain dopamine neurons, including imaging measures using Beta-CIT, silver staining to detect axonal damage and assessment for glial fibrillary acidic protein (GFAP) (Ricaurte et al. 2002). On the basis of this data, the authors speculate that ecstasy users are at risk of developing parkinsonism, either soon after use or as they age. However, considering the high mortality rate associated with this repeated dose regimen and the failure of studies in human users to find similar damage to dopamine neurons (Kish et al. 2000; Reneman et al. 2002; Semple et al. 1999) call to question the generalizability of these findings. A commentary appearing in the same publication describes the research and presents remarks made by other researchers, including a researcher who disagreed with the interpretation of the study findings (Holden 2002). MAPS issued a press release challenging the validity of these findings, particularly with respect to speculations concerning human risk.

More on the Use of Beta-CIT (RTI-55) in Detecting MDMA Neurotoxicity

This report describes research in rhesus monkeys and rats intended to assess the ability of the radioligand Beta-CIT to detect MDMA-associated reductions in 5-HT by comparing baseline SPECT Scans with scans performed after MDMA treatment in monkeys, and by using autoradiography procedsures in rats. (Autoradiography was also used in monkeys as well.) It appears that specific binding from Beta-CIT decreased after treatment with MDMA, with the decrease greatest four days after treatment, and with binding increasing again 31 days after MDMA treatment. Howeverk there was some indication that striatal dopamine was also reduced after MDMA administration, with reduction in DA binding growing stronger 31 days after MDMA administration. Overall, these studies suggest that Beta-CIT is able to detect reduction in serotonin transporter, but that it probably is not distinguishing between destruction of transporter sites and reduction of sites produced through other means.