In November, 2002, 2 studies of ecstasy, 2 reports on demographics and drug use, 1 review paper, 7 in vitro and non-human animal studies, and 4 forensic papers (not summarized) were located.

New Measure of 5-HT Function Tested in Ecstasy Users

Electroencephalography (EEG) and electro-oculography (EOG) conducted after administering the serotonin releaser dexfenfluramine failed to find all but one difference between men reporting moderate use, heavy use or no use of ecstasy (Gijsman et al. 2002). Dexfenfluramine produced even less slow-wave activity in heavy ecstasy users than in the other groups, but this finding was opposite that predicted by the authors. Since predictions of increased peak saccadic velocity after dexfenfluramine in all groups were confirmed, the authors believe they have devised a good method of measuring serotonin function.

Health Complaints: An On-Line Survey

Extent of self-reported ecstasy use, measured as number of uses in a lifetime, was associated with listing a greater number of physical and mental health complaints that respondents attributed to ecstasy use (Parrott et al. 2002). Self-reported complaints associated with extent of ecstasy use included changes in mood (greater anxiety, depression), reduced memory and other symptoms than those who had used ecstasy 9-99 times, and people using 1-9 times were least likely to report these problems. It is difficult to draw conclusions from this study for a variety of reasons, including issues of independent diagnosis of complaint, influences of respondents' beliefs concerning the negative effects of ecstasy use on health, and failing to test for effects due to use of other drugs. This last issue may be important given that polydrug use itself is associated with increased health complaints (e.g. Parrott et al. 2001).

Demographics

An analysis of data drawn from Monitoring the Future survey collected from 1996 to 1999 found that high school seniors reporting ecstasy use in the last 12 months were likely to be White than would be predicted through examining the racial distribution of each sample (Yacoubian et al. 2002).

Review

An analysis and review of harm reduction programs discussed the benefits of presenting drug-related harm minimization information within the context of harm minimization and health information relevant to nightclub or rave environments (Bellis 2002). The author argues that such a presentation will reduce resistance to providing this information among various community and government groups. Comparative figures for drug use, including ecstasy use, are also provided.

Measures of and Markers for MDMA Neurotoxicity

The validity of the radioactive compound Beta-CIT (RTI-55) as a measure of MDMA neurotoxicity was assessed by comparing the effects of p-chlorophenylalanine (serotonin synthesis inhibitor) and MDMA treatment on cortical and hippocampal serotonin in rats (Boot et al. 2002). Serotonin and 5-HIAA content in p-chlorophenylalanine-treated rats was even lower than in MDMA-treated rats, but only MDMA reduced Beta-CIT binding, both immediately after and up to 14 days after treatment. In another study in rats, release of serotonin (5-HT) and dopamine (DA) were assessed in rat synpatosomes (in vitro constructions retaining properties of synapses) and in-vivo, with microdialysis. The authors propose that ability to cause release in synaptosomes be considered a marker of potential neurotoxicity in substituted amphetamines (Gobbi et al. 2002). MDMA and p-pCA both released 5-HT in synaptosomes, whereas MTA and mCPP failed to release serotonin in vitro despite doing so in vivo. However, it is unclear whether these findings are generalizable to other compounds, such as fenfluramine.

Neurotoxicity in Rats: Three Models

Several models of MDMA neurotoxicity were tested either directly or indirectly, sometimes with conflicting results. For instance, one study reported that contrary to expectations, reducing amounts of the cellular "fuel" glucose through 2-DG not only failed to exacerbate MDMA neurotoxicity in rats, but seemed to attenuate reductions in brain serotonin (Yuan et al. 2002). While the effects may be due to relationships between body temperature and metabolism, 2DG still did not enhance fenfluramine neurotoxicity, a substituted amphetamine that is neurotoxic without inducing hyperthermia. Another research team posited and found some evidence for the existence of a highly reactive metabolite of serotonin that they believe could interfere with cellular respiration (Jiang et al. 2002). However, they have yet to test this model in relation to MDMA neurotoxicity. Lastly, researchers found that reducing dopamine (DA) release through the use of dopamine transmitter "antisense" (RNA that interferes with the expression of the dopamine transmitter) produced a neuroprotective effect striatum, but not hippocampus in rats (Kanthasamy et al. 2002). Dopamine transmitter antisense reduced signs of MDMA neurotoxicity without altering body temperature.

Liver and Kidney Cells and MDMA

An in-vitro study of the effects of MDMA on cultured rat liver cells found that very high doses of MDMA produced signs of apoptosis, or programmed cell death (Montiel-Duarte et al. 2002). However, as has been the case in previous papers published by the same research team (e.g. Beitia et al. 2000), the doses used were 3 to 11 times those expected in humans, and so it is unclear whether study findings are useful in examining possible causes of hepatotoxicity in humans. Another in-vitro study of cultured rat and human kidney cells failed to find any nephrotoxic (kidney cell damaging) effects of MDMA or MDA, even at very high concentrations (Carvalho et al. 2002). However, the researchers did find that the potential MDMA metabolite alpha-methyldopamine, and other potential MDMA metabolites did produce some damage to kidney cells, though again at very high concentrations. It should be pointed out that kidney damage after ecstasy use that is not associated with hyperthermia or other adverse events is rare.