Two studies of ecstasy users, 2 studies of ecstasy user demographics, 5 review papers, 1 investigation of harm reduction strategies, 1 case report, and 9 in-vitro or non-human animal studies were located in August 2002. Four forensic and chemistry papers were also located in this time period, but are not summarized.

Teeth and NK Cells

University students who reported using ecstasy and stimulants showed greater tooth wear on their first lower molars than age and age and gender matched controls attending the same university, and there was a trend for greater wear on the upper first molars as well (Nixon et al. 2002). Though the sample size employed was small (13 ecstasy users versus 13 controls), study findings suggest that people regularly using substances that promote bruxism (teeth grinding) may experience greater risk for dental wear. A study of male ecstasy users in Spain found that regular ecstasy use was associated with lower numbers of several types of immune cell, including natural killer (NK) cells, T cells and CD4 cells (Pacifici et al. 2002; Study 1). A longitudinal study comparing a sub-sample of 8 ecstasy users with controls found that number of lymphocytes was lower in this sample 1 year later, and that B cells and CD4 cells were lower than baseline 2 years later, with low numbers of NK cells found at all points in time (Pacifici et al. 2002; Study 2). It would appear that regular ecstasy use leads to impairment of some immune function over time.

Demographics and Harm Reduction

A report on drug use in female adolescents diagnosed with eating disorders (Stock et al. 2002) and drug use patterns in South Africa (Parry et al. 2002) both included information on ecstasy use in these populations. Attitudes toward harm reduction posters and pamphlets were assessed in a target population (London dance event attendees) and in the general population (through a telephone hot-line) in a study published in 1999 (Branigan and Wellings 1999). Attitudes toward the campaign literature were generally positive, and very little negative feedback was received. Data gathered from focus groups of Scottish ecstasy users reported that users recognized risks of ecstasy use and made attempts to manipulate set and setting in order to reduce them (Shewan et al. 2000). Participants in these focus groups made efforts to improve good set, reduce risks of purchasing fake pills and reduce the risk of short-term risks of use, but did not address potential long-term risks of use.

Reviews

Three of 5 reviews found covered specific areas of research, such as investigations into arginine vasopressin release after MDMA in humans or in cultured rat brain (Fallon et al. 2002), acute immunological effects of MDMA in humans and long-term effects of ecstasy use (Pacifici et al. 2002) and the therapeutic and adverse effects of various serotonin releasers, including MDMA (Rothmann and Baumann 2002). The remaining 2 reviews consist of a chart comparing mostly substance-related deaths in England and Wales (McKenna 2002) and a poorly-written review of psychiatric symptoms associated with ecstasy use (Montoya et al. 2002).

Case report

A case of catatonia after ecstasy use is reported. The patient recovered within 3 weeks; the presence of MDMA in blood or urine was never established.

Pharmacology-Metabolism in Brain and Elsewhere

A microdialysis study comparing the effects of PMA, MDMA and methamphetamine in rat caudate found evidence that PMA acts as a monoamine oxidase inhibitor (MAOI) because lower concentrations of neurotransmitter metabolites were found after PMA than after MDMA or methamphetamine (Gough et al. 2002). These findings may offer one explanation for why PMA is associated with a far greater number of adverse events than either MDMA or methamphetamine. The role of the enzyme CYP2D6 and its variants in the metabolism of MDMA is examined in cultured human liver cells and (Ramamoorthy et al. 2002), and found that some variants metabolize MDMA more readily than others; however, at higher doses, MDMA probably inhibits CYP2D6, rendering genetic variations in CYP2D6 function less relevant in the metabolism of higher doses of MDMA.

Acute Effects of MDMA in Rats and Mice

The cannabinoid system altered the rewarding properties of intracerebral (ICV) MDMA, as established in a study in rats trained to press a lever to receive ICV MDMA (Braida et al. 2002). A cannabinoid agonist seemed to enhance the rewarding properties or intensity of MDMA, and a cannabinoid antagonist decreased the rewarding properties of ICV MDMA. An examination of how different serotonin receptors affected MDMA-induced increases in activity and the rewarding effects of MDMA and relying on receptor antagonists found that 5HT2C receptors attenuated MDMA-induced hyperactivity and reduced the rewarding effects of MDMA (Fletcher et al. 2002), perhaps through altering dopamine release. It is unclear whether 5HT2C receptors have similar effects on the stimulant-like effects of MDMA in humans. An investigation into the acute effects of MDMA in ÒadolescentÓ mice (Morley-Fletcher et al. 2002, see also ÒNeurotoxicityÓ) found that MDMA produced analgesia when administered at 38 or 52 days after birth, but not at 28 days.

Developmental Effects of MDMA in Rats and Mice

Investigations into the neurotoxicity of MDMA in fetal mouse cells and in neonatal rats arrived at somewhat contradictory findings (Meyer et al. 2002; Won et al. 2002). Whether housed in a less warm (31 deg. C) or warmer (37 deg. C) environment, and in contrast with earlier findings, Meyer and colleagues found that serotonin neurotoxicity was seen in neonatal rats, including those killed 56 days after the last dose of MDMA. On the other hand, exposure to MDMA enhanced the development of serotonin and dopamine neurons, rather than harming dopamine neurons, as is usually the case in adult mice. Acute and long-term effects of MDMA were given at three points in mouse ÒadolescenceÓ (Morley-Fletcher et al. 2002). Findings indicate that rats were more social when given MDMA in ÒearlyÓ (28 days) or ÒlateÓ (52 days) adolescence, and that unlike adult mice, adolescent mice showed reduced serotonin after receiving MDMA.

Neurotoxicity: New and Different Models

A mouse model of MDMA neurotoxicity found that damaging norepinephrine neurons enhances MDMA neurotoxicity, suggesting a protective role for NE neurons (Fornai et al. 2002). While it is difficult to generalize from mice to humans, it is notable that MDMA has little effect on rat NE neurons as well. A link between stimulants and related drugs, including MDMA, and neurotoxicity in a brain stem area called the habenula fasciculus retroflexus is described, largely on the basis of examining the brains of rats after having given them amphetamine or cocaine (Ellison 2002). While effects of continuous amphetamine or cocaine administration are described, no other behaviors are associated with damage to this area of the brain.