Commentary on news coverage of ecstasy user/memory meta-analysis
Several news reports have appeared discussing a paper to be published in the journal Human Psychopharmacology finding that ecstasy use is related to impaired verbal memory, but not impaired visual memory. This would hardly be newsworthy, considering the history of previous ecstasy user studies, except that this paper examined over 600 people. Some news reports even state in headlines that taking ecstasy once can impair verbal memory. However, this claim is unfounded and cannot be made on the basis of this study.
What is not made clear in all news reports, though some do note it, is that the study is a meta-analysis. That means that the authors are combining data from already-published studies in a way that lets them treat it as if it were one large sample. This meta-analysis relies on previous retrospective studies of ecstasy users. This also means that the findings are not especially surprising, given that the majority of retrospective studies reached this conclusion, with or without additional qualifiers
The meta-analysis is drawing on data from retrospective studies that already have methodological problems. Specifically, polydrug use is a strong confound in nearly all comparisons of ecstasy users, with very few studies able to find people whose use of alcohol and other substances matches that of ecstasy users (Gouzoulis-Mayfrank et al. 2006). Studies with well-matched controls tend to find fewer differences between ecstasy users and non-users (Halpern et al. 2004). As well, all retrospective studies raise issues of pre-existing differences between people who use ecstasy, especially regularly, and people who don’t. For instance, there is some indication that people who use ecstasy regularly may have psychological problems before they even start using it (Huizink et al. 2006). To learn something new, researchers have already started to turn away from retrospective to prospective studies that assess people before and after using ecstasy.
Previously, some researchers had assessed people who had never taken ecstasy before before and after receiving 1.5 mg/kg MDMA, and they presented this data at a conference (Ludewig et al. 2003). Another prospective study found differences in people who used ecstasy versus those who did not, but performance in both groups was within the normal range and we have raised questions about aspects of this report (Schilt et al. 2007). As well, preliminary observations of memory tests performed at the start and the end of Michael Mithoefer’s study do not indicate impaired memory after two sessions of MDMA-assisted therapy
As well, very few studies have attempted to assess the identity or purity of the street ecstasy people were taking, and when one research team attempted to do this, they found that even people convinced they were only taking MDMA were in fact taking MDA and amphetamine as well.
Some news reports note that the minimum lifetime dose for the entire collection of 26 studies was 16 tablets, and average lifetime use is over 300 tablets. That means that the findings do not apply to light ecstasy use. Certainly none of the studies investigated the effects of a few doses of MDMA as would be seen in clinical trials. The authors did not find a relationship between lifetime ecstasy dose and degree of verbal memory, but this does not mean that even light ecstasy use can impair memory. As noted above, use of other substances or pre-existing problems might be involved, and given the minimum versus average lifetime use, the sample likely contains more heavy than light users to start with. I will have more to say on the paper after a thorough reading of the paper, but a cursory glance suggests that the authors are more aware of the problems with retrospective studies in ecstasy users than the journalists covering the study, as they mention the problem of polydrug use in ecstasy user research.
However, after reading more detailed news reports, I conclude that there is nothing alarming within this meta-analysis and little that is genuinely new. It does not
Gouzoulis-Mayfrank E, Daumann J. (2006) The confounding problem of polydrug use in recreational ecstasy/MDMA users: a brief overview. J Psychopharmacol 20(2):188-93.
Commentary noting polydrug use as confound
Halpern JH, Pope HG Jr, Sherwood AR, Barry S, Hudson JI, Yurgelun-Todd D. (2004) Residual neuropsychological effects of illicit 3,4-methylenedioxymethamphetamine (MDMA) in individuals with minimal exposure to other drugs. Drug Alcohol Depend 75(2):135-147.
Samples matched on drug use, no memory impairment overall, only heavy users show some executive function (decision making and planning) problems.
Huizink AC, Ferdinand RF, van der Ende J, Verhulst FC. (2006) Symptoms of anxiety and depression in childhood and use of MDMA: prospective, population based study. BMJ 332(7545):825-828. Epub 2006 Feb 24
Prospective study in representative sample indicating that children with some psychological problems are more likely to start using ecstasy later in life.
Ludewig S, Ludewig K, Hasler F, Vollenweider FX (2003) No lasting effects of moderate doses of MDMA (Ecstasy) on memory performance and mood states in health humans. Biol Psychiatry 53 (Suppl); 205S. Data presented at the 58th Annual Conference of the Society for Biological Psychiatry, San Francisco, CA.
Presentation of data from prospective controlled trial
Schilt T, de Win MM, Koeter M, Jager G, Korf DJ, van den Brink W, Schmand B. (2007) Cognition in novice ecstasy users with minimal exposure to other drugs: a prospective cohort study. Arch Gen Psychiatry 64(6):728-736.
Third NeXT team study
Commentary and report on Schilt et al. 2007
Verbaten MN. (2003) Specific memory deficits in ecstasy users? The results of a meta-analysis. Hum Psychopharmacol 18(4):281-290.
Initial meta-analysis performed on 10 ecstasy user studies
Update: After viewing the publication, I learned that the minimum dose was 16 and not 19 tablets.