The Second Prospective Study of Ecstasy Users

The Second Prospective Study of Ecstasy Users: No Support for Changes in Brain Activity, Associative Memory or Selective Attention. By Ilsa Jerome, Ph.D.

Ilsa Jerome
May 2007

New research just published electronically suggests that using a couple of tablets of ecstasy doesn’t impair working memory or selective attention, and it doesn’t alter brain activity during attention or memory tasks (Jager et al. 2007A). In a previous publication, the same team of researchers from the Netherlands reported that low levels ecstasy use failed to produce any increases in chemical markers for neuronal injury and changed cerebral blood volume in only one brain area (de Win et al. 2007). Now the “Netherlands XTC Toxicity” (NeXT) team reports that comparing performance and functional magnetic imaging (fMRI) brain scans before and after ecstasy use, and making the same comparisons in people who chose not to use ecstasy in the first prospective study found that low doses of ecstasy did not change users’ brains. While these researchers did find that heavy users’ brains behaved somewhat differently from those of non-users in another recent report (Jager et al. 2007B), these differences were small and it appears that other drugs, including cocaine, amphetamine and tobacco, also affected brain activity.

The researchers scanned people before and after they stated they had used no more than ten tablets of ecstasy. Twenty-six “incipient” ecstasy users and 24 non-ecstasy using controls took part in this study, and both groups were scanned twice, once before anyone had used ecstasy, and again soon after a participant reported their first ecstasy use or at a similar time for a non-user control. The post-ecstasy scans happened on an average of 11 to 12 weeks after people reported using an average of 2 tablets (range 0.5 to 6, median 1.5 tablets; one participant reported having used 20 tablets). During the fMRI scan, all participants performed three different tasks. In one, they learned visually-presented strings of letters and indicated whether other letters belonged to the string. In another task, they had to identify “oddball” (different) tones or dots. They saw and heard both tones and dots, but they were instructed to ignore one modality (sound or vision) and attend only to the other. In the third task, participants learned pairs of pictures and indicated whether a pair of pictures matched the pair they learned. The researchers developed regions of interest (ROIs) through working with the group map for each of the three tasks, and then set out to see whether using ecstasy impaired memory or attention, and whether it also altered brain activity occurring during the memory and attention tasks.

The researchers failed to spot any significant interactions between time of measurement and group for performance on any of the three tasks, suggesting that using ecstasy did not affect performance. Furthermore, while the authors established separate ROIs for each task, they failed to find any differences between post-ecstasy brain activity in these light ecstasy users or non-user controls, aside from a “marginal” effect of differing use of hippocampal and parahippocampal areas for the picture recall task only, and then only when the researchers included the individual who had used twenty tablets. In all other cases, the two groups did not have any significantly different brain activity during selective attention or working memory tasks.

Like their first report examining people’s brains before and after the first few uses of ecstasy, this report failed to find support for claims that only a “single dose” of ecstasy can have long-term effects on cognitive function or brain activity. By contrast, a retrospective study using the same tasks and fMRI scans in a sample largely made up of heavy ecstasy users found that ecstasy use explained some variance in visual working memory, albeit very little (1%), and they spotted changes specific to ecstasy use in left dorsolateral prefrontal and right middle occipital areas (Jager et al. 2007B). Hence it seems that changes in brain function only occur after extensive use, and may be due in part to use of other substances. Jager and colleagues also found that amphetamine, cocaine and tobacco use were associated with differences in brain activity when people performed visual memory task, with amphetamine producing effects opposite to those seen after heavy ecstasy use.

The sample sizes in these studies are relatively small, and it is possible that the demanding nature of the study design resulted in selecting people who were doing better than the average polydrug and ecstasy users. Nevertheless, prospective studies offer great advantages over retrospective studies, and both of the two prospective studies suggest that low levels of ecstasy use have little to no effect on brain or cognitive function.


de Win MM, Reneman L, Jager G, Vlieger EJ, Olabarriaga SD, Lavini C, Bisschops I, Majoie CB, Booij J, den Heeten GJ, van den Brink W. (2007) A prospective cohort study on sustained effects of low-dose ecstasy use on the brain in new ecstasy users. Neuropsychopharmacology. 32(2): 458-470. Epub 2006 Nov 1.

Jager G, de Win MM, Vervaeke HK, Schilt T, Kahn RS, van den Brink W, van Ree JM, Ramsey NF. (2007A) Incidental use of ecstasy: no evidence for harmful effects on cognitive brain function in a prospective fMRI study. Psychopharmacology (Berl). May 3; [Epub ahead of print]

Jager G, de Win MM, van der Tweel I, Schilt T, Kahn RS, van den Brink W, van Ree JM, Ramsey NF. (2007B) Assessment of Cognitive Brain Function in Ecstasy Users and Contributions of Other Drugs of Abuse: Results from an fMRI Study. Neuropsychopharmacology. Apr 25; [Epub ahead of print]

Additional links

Special Report on De Win study triggered by press reports from a conference presentation

Open Letter from MAPS’ President Rick Doblin to NeXT study author Maartje de Win