One study in ecstasy users, one case study, one examination of ecstasy tablet content, and six in vitro and non-human animal studies in this time period.

Impaired Verbal Memory: None Found

Researchers who assessed memory with the Wechsler Memory Scale (WMS) in 40 ecstasy users (lifetime consumption = 258 +/- 574 ecstasy tablets) and 37 cannabis users matched on gender and education failed to find significant differences between the two samples on WMS scale scores (Simon et al. 2002). They only found a trend for ecstasy users to perform less well than controls on immediate and delayed auditory recall. Vocabulary, gender, age, use of cannabis and amphetamine, but not ecstasy use, were all predictors of performance on the WMS. This is one of a few published reports that did not find impaired memory in ecstasy users. It is notable that some of the other publications that failed to find impaired memory function in ecstasy users also used the WMS (e.g. Bolla et al. 1998).

Case Report

Ecstasy-related hyponatremia was reported in a 19-year old woman after consuming ethanol and one tablet of ecstasy approximately 12 hours prior to admission to hospital (Traub et al. 2002). The patient recovered in 48 hours.

Ecstasy Tablets in Northwest England

Amount of MDMA (in milligrams) detected in 136 samples gathered from police drug seizures in the Northwest of England in 2001 was 60 to 69 mg. Average MDMA content in a sample of "White Dove" tablets was 78.8, with MDMA contents assessed in 80 randomly selected tablets from this sample, also obtained from a police seizure (Cole et al. 2002). Comparisons with other studies indicate that MDMA content has declined from levels in the early 1990s.

Anxiety, Cardiovascular effects in Mice

Research assessing the effects of MDMA on anxiety in mice found that mice behaved more anxiously when placed in the elevated plus maze after one dose of MDMA (8 or 15 mg/kg) and after a repeated dose regimen of 5 single, daily doses (1 or 8 mg/kg) (Navarro et al. 2002). More anxious behavior was recorded after repeated doses than after single ones. However, mice behaved less anxiously after repeated doses of 15 mg/kg. Since serotonin levels were not measured in these mice, study findings cannot be used to establish a link between anxiety in rodents and neurotoxicity. An assessment of mean arterial pressure after 10 minutes of 5 or 20 mg/kg MDMA in mice with and without alpha2 adrenergic receptors (knockout mice) found that the alpha2 receptor knockout mice lacked the depressor effect that followed the pressor effect in "wild-type" mice, and that the pressor effect lasted far longer (Vandeputte et al. 2002). Administering an alpha2 receptor antagonist (BRL44408) to wild-type mice produced similar effects to those seen in knockout mice. Study findings suggest that MDMA has some alpha2 activity. It should be noted that humans have elevated blood pressure after MDMA (e.g. Grob et al. 1996; Lester et al. 2000; Mas et al. 1999; Tancer and Johanson 2001; Vollenweider et al. 1998).

First Gene Expression Portrait

Researchers examining the effects of a single 20 mg/kg dose of MDMA on gene expression in rat frontal cortex over a span of about a day (and 7 days later) found that MDMA upregulated expression of 19 genes and downregulated expression of 9 genes (Thiriet et al. 2002). The researchers identified five different clusters of genes, defined by time course and direction of regulation. Clusters included a group of genes expressed immediately after MDMA (Clusters B and C), and another group of genes that showed increased or decreased expression 4 hours to 1day later (Clusters A and B). Genes relating to serotonin 3 receptors, immune function and neuroplasticity were among those activated by MDMA. Since this is one of the first studies of the effects of MDMA on gene expression, it is difficult to estimate the significance of study findings or to interpret their relevance for humans.

Neurotoxicity and Cognitive Function in Monkeys

The effects of a neurotoxic dose regimen of MDMA (10 mg/kg daily for 4 consecutive days) on brain serotonin and cognitive performance was assessed in rhesus monkeys (Taffe et al. 2002). Despite sustaining up to 76% to 93% loss of serotonin in all cortical areas, MDMA-treated animals did not perform differently from controls on a comprehensive test battery designed to measure memory, attention and dexterity in primates. There were also no differences in test performance between MDMA-treated monkeys and controls after challenge with 8-OH-DPAT (a 5HT1A agonist) or the 5HT2A antagonist ketanserin. However, MDMA-treated monkeys were more sensitive to the attention-disrupting and rate slowing effects of challenge with m-chlorophenylpiperazine (mCPP), a serotonin releaser and 5HT2C agonist. This study suggests a possible dissociation between MDMA neurotoxicity and effects on cognitive function supported in earlier studies (Winsaur et al. 2002; Frederick et al. 1998).

Neurotoxicity in Rodents-Developmental Effects, Circadian Rhythm Effects

Researchers assessing the effects of a single dose of 5, 15 or 20 mg/kg MDMA on circadian rhythm in Syrian hamsters found that MDMA attenuated phase advance produced by the 5HT1A/7 agonist 8-OH-DPAT (Colbron et al. 2002). MDMA also reduced phase advance after a 15-minute pulse of light presented after keeping hamsters in total darkness for 7 days, and immediately after lights-off in a normal 14: 12 light-dark cycle. Though brain serotonin or other markers of serotonin function were not measured, the authors interpreted their findings as demonstrating an association between MDMA neurotoxicity and changes in circadian rhythm. No studies have assessed changes in circadian rhythm in ecstasy users. Research employing prenatal and neonatal exposure to MDMA in rats suggests that MDMA reduced brain serotonin when exposure occurred prenatally (20 mg/kg twice daily for 4 days starting on gestational day 15) or after an identical regimen was administered, starting on postnatal day 25 (Kelly et al. 2002). Developmental effects were measured by examining serotonin function (through paroxetine binding) and glucose metabolism. Because the authors did not measure hyperthermia in dams (pregnant female rats) or neonates given MDMA, it is possible that this critical period arises as a result of changes in thermoregulation, and neonates were unaffected by MDMA because they failed to become hyperthermic.