One human trial, consisting of two studies, 3 studies of ecstasy users, 5 studies of ecstasy user demographics, 5 papers addressing other areas of ecstasy use (such as harm reduction strategies), 8 reviews, 5 in vitro and non-human animal studies and 4 forensic or chemistry studies were located during this time period.

MDMA Metabolism in controlled and uncontrolled situations

Metabolism and drug detection in various bodily fluids after 75 mg MDMA was measured in 12 men and women, all experienced ecstasy users (Samyn et al. 2002; Study 1). MDMA was detected in blood, urine, sweat and saliva, with sweat containing the lowest concentrations of MDMA. Salivary MDMA concentrations varied more widely between subjects than did concentrations of MDMA in blood, with concentrations in both fluids most similar 1 h post-drug and least similar at 5 h post-drug. A second uncontrolled study of detection of self-administered ecstasy tablets in urine and saliva found that MDMA and related drugs (MDE, amphetamine) were mostly detectable in both urine and saliva, though in 2 cases drugs were detectable in urine only (Samyn et al. 2002; Study 2). This was true of measurements taken 1 hour after self-administration and between 4 and 6 hours after initial measure. MDMA is apparently detectable in saliva and sweat as well as blood and urine, as also seen in studies like those of Picchini et al. (2002).

Neuroendocrine challenge, ecstasy use and psychiatric diagnosis

When compared with gender-matched non-drug using controls, male ecstasy users showed blunted growth hormone response after challenge with the dopamine agonist bromocryptine without showing any differences in prolactin release (Gerra et al. 2002). The authors interpret these responses as evidence that ecstasy use altered the dopamine system, but acknowledge that ecstasy use might alter 5HT2A receptors, and that changes in these receptors might be responsible for blunted response to bromocryptine. Ecstasy users in this study had higher depression ratings on two measures of depression. When considering these findings, it is important to note that study participants were selected from among those contacting a drug dependence clinic. Researchers in Germany found that ecstasy use was associated with diagnosis with a mental disorder in a representative sample of Munich residents aged 14-24 (Lieb et al. 2002). However, they also found that mental disorders, particularly other substance use and anxiety disorders, were more likely to precede ecstasy use than ecstasy use was to precede mental disorders. Though they also found an increase in some mental disorders after ecstasy use, all findings taken together suggest that the link between drug use and psychiatric problems is not simple.

Ecstasy use and attention

Ecstasy users and matched polydrug user controls performed similarly on a comprehensive test of attention, with the exception of one measure of sustained attention, wherein ecstasy users fared less well than polydrug user controls (Zakzanis et al. 2002). Performance on other sub-tests was inversely related other parameters of ecstasy use, such as lifetime dosage, yet no group differences were detected on these same tests. The researchers conclude that either ecstasy use or another variable associated with it (such as concurrent use of other drugs) may mildly impair attentional processes. Despite these findings, it appears that regular use of ecstasy and related drugs does not affect attentional processes.

Demographics of Ecstasy Use

The demographics of ecstasy use in several different populations were explored, including methamphetamine users in the Los Angeles area (Brecht and Mayrhauser 2002), dance event attendees in Montreal (Gross et al. 2002), high school students (Yacoubian 2002b) and juvenile offenders (Yacoubian et al. 2002a). Self-reported ecstasy use was common at dance events, and individuals reporting both methamphetamine and ecstasy use fit the profile of young polydrug users. Juvenile offenders reporting ecstasy use were more likely to be White and less likely to be attending school. Ecstasy use in high school was associated with being unsupervised by parents or others and with polydrug use.

Two policy papers

Two policy papers were written by people associated with MAPS. In one, Baggott argues for a harm reduction strategy for ecstasy users focusing on reducing common complaints, and not rare adverse effects or long-term effects (Baggott 2002). In the other paper, MAPS' President describes a clinical plan for the development of MDMA-assisted psychotherapy as a treatment for PTSD (Doblin 2002).

Pill content, acute negative psychological effects, case series of fatalities The accuracy of various methods for detecting fake pills is addressed in a review and discussion of material misrepresented as MDMA (Hayner 2002); a review of reports of pill contents conducted by the author found that approximately 60% of pills sampled contained MDMA or a related substance. The author concludes that neither home testing kits nor laboratory tests are sufficiently accurate, but does not submit a more accurate means of detection. An examination of qualitative data gathered from ecstasy users in Northern Ireland suggests that set, setting and material all play a role in negative psychological effects (McElrath and McEvoy 2002). Use of psychoactives in other cultures and situations are compared with the current setting and culture surrounding drug use in North American and Europe (Nencini 2002; from abstract only). A case series of fatalities related to amphetamines or ecstasy use in Northern Greece is reported (Raikos et al. 2002), with the case series similar to those presented elsewhere except for the higher frequency of drowning as cause of death and an older average age of death.

Reviews

Only two generalized reviews of MDMA or ecstasy were located during this time period (Freese et al. 2002; Gowing 2002), and only one has been summarized. All other reviews were subject specific. Reviews included a critique of inflated claims of risk associated with MDMA, in particular as relates to cognitive function (Cole et al. 2002a), critiques of this review (Croft 2002; Morgan 2002; Parrott 2002) and a reply to the critiques (Cole et al. 2002b), a review of demographic information pertaining to ecstasy use in the United States (Landry 2002), a review of the history and sociology of MDMA use with a focus on media coverage (Rosenbaum 2002), and an overview of a series of trials of MDMA in humans (Vollenweider et al. 2002).

MDMA Actions in Rats

An in vitro study in rat synaptosomes and aortic tissue found that MDMA, 4-MTA and 4-MTMA all released 5-HT from synaptosomes, with MDMA releasing the most 5-HT (Murphy et al. 2002), but unlike the thioamphetamines, MDMA failed to enhance serotonin-induced contractions of aortic tissue. The authors concluded that MDMA is far less active at non-neuronal 5-HT transport sites than it is on brain 5-HT transporter. Another study in rats examined expression of the preprotachykinin A gene in rats after MDMA (Pompei et al. 2002), assessing social memory through two presentations of the same "stranger" rat. Gene expression was reduced specific brain areas (nucleus accumbens, dorsal-posterior amygdala and others) and increased in other areas (caudate). MDMA-treated rats may have shown an acute reduction in social memory, but the measure used may also be affected by an MDMA-induced increase in social activity.

Drug Discrimination Research

The use of "differential outcome" training (pairing a stimulus with a specific outcome, as in associating MDMA with one taste and amphetamine with another) was examined as a means to speed learning in a 3-lever drug discrimination test in rats (Goodwin et al. 2002). Contrary to the authors' predictions, pairing different tastes or different pre-reward cues (such as lights or tones) with different drugs did not increase learning to discriminate between two drugs and saline (MDMA and amphetamine in the first study and MDMA and LSD in the second study).

MDMA Effects on the Cardiovascular System and Heart

A replication of an earlier study conducted by the same research team (Gesi et al. 2002a), found that exposing mice to MDMA and loud noise produced ultrastructural changes at the mitochondrial level of cardiac tissue, including disorderly arrangement of cristae and a less dense matrix (Gesi et al. 2002b). Changes were only observable under electron microscope. As previously noted, it seems likely that exposure to loud noise is stressful for mice but enjoyable in humans, and so findings may not be generalizable to humans. Another study examined the effects of 3 intermittent 4-day binges on cardiovascular response in rats (Badon et al. 2002). Their findings suggest that MDMA exerts cardiovascular effects mostly through the sympathetic system, and heart inflammation was seen in rats given all three repeated dose regimens, intended to model human "binges." However, dose regimens in this study lasted longer than most human binges. Somewhat surprisingly, continuous monitoring of cardiovascular function indicated slow heart rate (bradycardia) and hypotension at the start of drug effects for each dose regimen; the authors speculate that this relates to release of peripheral stores of 5-HT.