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The MDMA page of Wikipedia currently states:

A meta-analytic review of the published literature on memory show that ecstasy users may suffer short-term and long-term verbal memory impairment—with 70–80% of ecstasy users displaying impaired memory. Other meta analyses have reported possibility of impairment of executive functioning.

Please assess these claims.

17

We don't know conclusively one way or another.

A recent 2011 study [Full PDF Version] completely contradicts most of the previous research on the topic. My previous answer (left intact below) probably cited studies that used unintentionally biased groups of "users" and "non-users".

Specifically, this new study released compared only those people associated with the 'rave' subculture. They selected participants based on the number of times they had participated in all-night raves and their levels of drug use, and thoroughly drug tested those participants who claimed no use of ecstasy. They found:

In contrast to many prior studies, ecstasy users in the new study showed no signs of cognitive impairment attributable to drug use: ecstasy use did not decrease mental ability.

(emphasis mine)

From this article summarising the study:

The researchers fixed four problems in earlier research on ecstasy. First, the non-users in the experiment were members of the "rave" subculture and thus repeatedly exposed to sleep and fluid deprivation from all-night dancing -- factors that themselves can produce long-lasting cognitive effects.

Second, participants were screened for drug and alcohol use on the day of cognitive testing, to make sure all participants were tested while 'clean'. Third, the study chose ecstasy users who did not habitually use other drugs that might themselves contribute to cognitive impairment.

Finally, the experiment corrected for the possibility that any cognitive impairment shown by ecstasy users might have been in place before they started using the drug. The resulting experiment whittled 1500 potential participants down to 52 carefully chosen ecstasy users, whose cognitive function was compared against 59 closely-matched non-users, with tests administered at several stages to make sure participants were telling the truth about their drug and alcohol use.

Whether or not the results of a ~100 person study are compelling I could not say - there have been other studies released since showing decreased brain mass cognitive impairment. What I can say is that whether a participant has frequently participated in all-night dancing (dehydration, sleep deprivation) is absolutely a factor that should be included in any studies on the drug. Either long term studies with higher numbers of high-use participants, or a meta-analysis is required to draw a conclusion one way or another.

The study itself also cautions that it did not include any long-time heavy users (emphasis mine):

On one hand, it is possible that ecstasy indeed causes residual cognitive neurotoxicity, albeit perhaps only in individuals with high-level exposure, or with possible co-factors predisposing them to ecstasy-induced neurotoxicity. If so, we might have failed to detect a difference when a true difference exists, perhaps because we evaluated only six participants with very high ecstasy exposure (≥150 life-time episodes) or perhaps because our population included few individuals with vulnerability-inducing cofactors.


(Original Answer)

This UNSW study was performed solely to assess the impact on prospective memory (remembering to perform a planned action or intention at the appropriate time):

There is considerable evidence that 3,4-methylenedioxymethamphetamine (MDMA; a principal ingredient in the popular recreational drug “ecstasy”) is a serotonergic neurotoxin that leads to degeneration of serotonergic axon terminals in animals, including nonhuman primates (Buaumann et al. 2007; Scheffel et al. 1998). The neurotoxic effects of MDMA appear to be long-lasting, with serotonergic depletion in one study shown 7 years after initial administration of the drug (Hatzidimitriou et al. 1999). It has been argued that these neurobiological changes underpin the well-documented neurocognitive deficits associated with MDMA use in humans (Morgan 2000).

The Morgan study mentioned there (sorry, paywall) states:

deficits in memory performance in recreational ecstasy users are primarily associated with past exposure to ecstasy, rather than with the other legal and illicit drugs consumed by these individuals, and are consistent with reduced serotonergic modulation of mnemonic function as a result of long-term neurotoxic effects of MDMA in humans.

And the result of the UNSW study was in keeping with your quoted figure:

Ecstasy users were significantly impaired on Virtual Week, and these deficits were of a comparable magnitude irrespective of the specific prospective memory task demands. The pattern of results was unchanged after controlling for marijuana use, level of psychopathology, and sleep quality. Further, prospective memory was shown to be significantly impaired for both relatively infrequent and relatively frequent ecstasy users, although for the latter group the magnitude of this deficit was greater.

Results by task type

  • 1
    Kudos for the contradictory update! – Cray Jun 15 '11 at 15:41
  • DEspite the confusing update, the studies are not either large enough or controlled enough to give really trustworthy results. And they contradict other work. I'd like to see a more comprehensive review. – matt_black Oct 14 '12 at 22:16
  • @BrendanLong fair point, updated. – jozzas Oct 20 '12 at 1:54
  • @matt_black I agree with that, I added to my answer that there need to be studies including longer term users or Cochrane-style reviews to draw a conclusion. – jozzas Oct 20 '12 at 1:55
2

In short: MDMA may have some effects, but they are likely small and reversible.

The trouble with much of the debate on the harms of MDMA is that the reporting is very biased and the underlying scientific studies are often not very good. So it isn't that difficult to find many studies the show significant harm. But this is likely a poor summary of the totality of our knowledge.

One illuminating example that resulted in major headlines and some smugness from government advisors keen on fighting the war on drugs occurred in 2002. A paper was published in the prestigious journal Science, which suggested that monkeys suffered permanent brain damage from typical recreational human doses of the drug. This looked like the first really conclusive experiment validating the idea that MDMA caused permanent brain damage. Unfortunately, the paper had to be retracted because a lab error meant the monkeys had actually been given overdoses of methamphetamine not MDMA (while chemically related, methamphetamine is a much nastier drug). That retraction didn't get anything like the headlines of the original paper.

The New York Times report on the retraction noted some other issues with Dr. George A. Ricaurte's work:

It was not the first time Dr. Ricaurte's lab was accused of using flawed studies to suggest that recreational drugs are highly dangerous. In previous years he was accused of publicizing doubtful results without checking them, and was criticized for research that contributed to a government campaign suggesting that Ecstasy made ''holes in the brain.''

The rest of the article is illuminating for discussion about the uncertainties of MDMA research.

Reviews of the effects of MDMA have been conducted in the last few years. One such review by the ACMD (the Advisory Council on the Misuse of Drugs, the scientific body intended to advise the UK government about the science of drugs) concluded that the drug was far less harmful than cocaine and heroin and should be downgraded. The government ignored this advice. Later, David Nutt, the chairman of the ACMD was sacked by the government when he (perfectly reasonably on statistical grounds) pointed out that Ecstasy was less harmful than recreational horse riding (see Nutt's book).

It is worth quoting their summary of the literature and known science. All the following quotes are from (different sections of) the ACMD report.

A concern has been raised that extensive, chronic MDMA use can lead to clinical depression, perhaps through changes in brain serotonin function discussed in Section 6. The evidence is currently equivocal – most studies do not find significantly increased levels of clinical depression in current or ex-MDMA users...

...The effects of MDMA on psychomotor function have been studied during driving performance. Studies on MDMA alone have shown that it can improve some aspects of driving and impair others (Ramaekers et al., 2006; Kuypers and Ramaekers, 2008). This contrasts with alcohol which impairs on all measures and leads to impulsively impaired judgement...

...Like amphetamines, MDMA has been found to improve impulse control and sustained attention – an effect opposite to that of alcohol...

...Early rat studies on the pharmacology of MDMA found that as well as elevating serotonin it also damaged serotonin neurons (those that release serotonin) in the brain (reviewed by Green et al., 2003). Subsequent studies in non-human primates produced similar findings (Hatzidimitriou et al., 1999), although in mice dopamine neurons were also affected. Although the doses used in these studies were considerably higher than those typically taken recreationally, these preliminary findings raise concerns that MDMA might produce similar nerve cell damage in humans.10 However, a recent non-human primate study using dosing similar to that seen in humans showed no effect (Fantegrossi et al., 2004)...

...Statistically significant alterations in some brain-imaging measures have been reported. Their magnitude is generally less than comparable findings in alcohol, cocaine and methylamphetamine misusers and the clinical relevance of these findings is unclear...

A systematic review of the literature by Rogers et. al. in 2009 (which provided some of the ACMD's evidence) concluded that there seemed to be some consistent effects but that they were small. Moreover, many of the studies were poorly conducted and may be biased. In their words:

The evidence we identified for this review provides a fairly consistent picture of deficits in neurocognitive function for ecstasy users compared to ecstasy-naïve controls. Although the effects are consistent and strong for some measures, particularly verbal and working memory, the effect sizes generally appear to be small: where single outcome measures were pooled, the mean scores of all participants tended to fall within normal ranges for the instrument in question and, where multiple measures were pooled, the estimated effect sizes were typically in the range that would be classified as ‘small’.

However, there are substantial shortcomings in the methodological quality of the studies analysed. Because none of the studies was blinded, observer or measurement bias may account for some of the apparent effect. There is a suggestion of publication bias in some analyses, and we saw clear evidence of selective reporting of outcomes.

In summary: there appear to be some effects on cognition, but they are small and there is little evidence of permanence. Moreover, some of the observations may be a result of confounding or bias.

  • I don't mind down votes, but I like to know why. Help improve the answer by commenting, please. – matt_black Oct 15 '12 at 13:31
  • That was mine, because I have (unscientifically) seen the brain damage of ecstacy. This type of answer can lead people to use brain-damaging substances. It is hard to detect brain-damage in one's own self by introspection, the effects are usually only noticible in day-to-day life after they are already severe and irreversible, but I have no direct experience with ecstasy, I have never taken it, so I cannot be sure. I don't like this answer, because this is something that was said about many other drugs, all of which cause severe defects in high cognitive performance. Don't encourage people. – Ron Maimon Oct 17 '12 at 5:02
  • @RonMaimon That is exactly the sort of arguments governments use when prohibiting drugs. But it is often based on misattribution of the source of harm which is why reliable science needs to be done. Withholding information and prohibition don't stop people consuming drugs but lower the quality of the drug and obfuscate people's own risk judgement. Neither of these results minimises the harm caused. – matt_black Oct 17 '12 at 8:12
  • I agonized over the downvote because of this, but in the end, the onus is on the drug to prove itself safe: long-term users need to lead long productive lives with no ill effects. Only caffeine and nicotine have passed this test. People used to say small occasional doses of marijuana, LSD, cocaine, are harmless and in all these cases, the social experiment was done by self-experimenters over many decades, and the negative results were obvious and large. With MDMA, like most amphetamine derivatives, it doesn't even require very much to notice the impairement. – Ron Maimon Oct 18 '12 at 0:42
  • @RonMaimon I think we just disagree on the evidence. I want to see proper scientific studies not anecdotes. MDMA in particular has been traduced due to misidentification. Many of its supposed effects turn out to be from other substances (eg methamphetamine). Even the scientific literature has suffered from this misidentification, so you have to be really careful with the sources and quality of studies. – matt_black Oct 18 '12 at 9:12

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