Critique of Heffernan Ecstasy/Memory Study by Harry Sumnall (3/28/01)

"Escape into Ecstasy leaves gaps in reality"
"The drug that costs memories" (London Times)
"Regular Ecstasy users risk loss of memory" (Guardian)

Ecstasy users in the UK would be forgiven for thinking that they should add deja vu to 'cartilage in the brain' in the long list of items that researchers and the popular media have told them that they should be suffering from. Pilot data presented at the British Psychological Society meeting in Glasgow on Tuesday by Drs Heffernan, Scholey and Ling of the University of Northumberland seemed to offer yet more evidence indicative of deleterious effects of Ecstasy upon mnemonic function... so reported the UK press. Surprisingly, out of all the excellent pieces of work on show at the meeting it was Ecstasy research (again) that made the headlines. Perhaps a change in research focus would be the answer for all those other psychologists hoping to highlight their own interesting findings?

[My own pick of the research on offer was from the lab of Richard Dafters which presented more evidence for the effects of repeated administration of MDMA upon circadian rhythms; i.e the drug causes a shift in the body's circadian clock. Some researchers are of the opinion that it is this disruption in normal circadian rhythm which may contribute to the behavioral and cognitive differences seen in ravers (for want of a better word) and not just the consequence of drug induced neurotoxicity, if at all. However, these are still just hypotheses and need to be investigated further]

The venerable UK press reported the research indicated that Ecstasy users display memory defects in common with sufferers of Alzheimer's disease and that many "may also find it difficult to recognize friends from their primary school days". Furthermore both short and long term memory are affected which suggests a severity greater than that observed in AD. The research, according to interviews, also suggested that employers should be wary of recruiting Ecstasy users for fear of their lack of ability to do a good job because of defects in planning behavior. Harsh news indeed for the soon to be unemployed millions around the globe or the 13% of UK undergraduates who report using Ecstasy recreationally. Perhaps it is now time for UK Higher Educational Institutions to remove images of super clubs and hedonistic clubbers from their prospectuses for fear of contributing to this brain drain?

The work presented at the BPS meeting was an extension of an article soon to appear in the journal Human Psychopharmacology provisionally entitled ' Self reported prospective memory defects in MDMA ('ecstasy') users'. The experimental design reported at the meeting was, in effect, a replication of this earlier study so referring to the methods and procedures in this more informative source is probably more useful than a newspaper report, brief abstract or a careful worded press release. If the results are also typical of findings from Ecstasy users as a whole then it is also possible to generalize from one population to another. The scientific team obtained the same results for both studies, but as should be evident, replicating experimental results does not lead to a more accurate interpretation of results (this doesn't imply that you should accept that my own interpretation is *more* valid!).

Briefly, the team reported that compared to non-users, Ecstasy users (defined as taking the drug >10 times in the past month- so volunteers were taking it every 3 or 4 days - how ever did the researchers manage to catch their subjects when they weren't on a come-down phase?!) scored worse on all three subscales of the Prospective Memory Questionnaire (subsections are short term habitual, long term episodic and internally-cued). Prospective memory, in simple terms, concerns remembering to do something at a future point. This may be remembering to keep an appointment, locking the door,not forgetting what you are saying in the middle of a sentence and meeting friends. Volunteers were asked to complete a questionnaire asking them to relate how well they remembered to do things and the strategies they might employ to help them to remember to do things. The questionnaire generally referred to the preceding month.

Now, I'm sure a quick referral to the MAPS archives would reveal many arguments as to the difficulties in interpretation of retrospective human Ecstasy studies so I won't repeat them here, but most of them are relevant (possible intergroup personality and life style differences, the lack of urinalysis, no clear distinction as to the amount of elapsed time since previous drug use etc.). However, what troubles me about this work is the way in which the self-reported drug history of the 'Ecstasy' using group suggests a much more satisfying explanation for the group differences, that all the newspaper reports, indeed the study authors themselves did not refer to; for which the statistical control employed by the authors was not ideal. In essence, I believe that the 'Ecstasy group' was either intoxicated by marijuana or coming down from Ecstasy in the time period that they had to refer back to...

The number of units of alcohol and the number of cigarettes used in the last month are reported to the best of the participants' abilities but Ecstasy, marijuana and cocaine use is only referred to as the number of times used in the past month, not the amount consumed. This is important considering some of the control procedures employed. The authors used a common and useful statistical method called ANCOVA which is a test that identifies measurements termed covariates (in this case use of other drugs than Ecstasy) which may be related to the test score (i.e they affect reporting on the scale) but not the experimental treatment (i.e. use of Ecstasy in the past month). By including such concomitant measures in the analysis, residual variation can be reduced by the extent to which it is attributable to the covariates. In other words they statistically tried to minimize the effects of other drug use upon self-reported test scores. The authors concluded that use of other drugs did not play a part in their results. Now this assumption itself is controversial considering potential drug-drug interactions upon neurotoxicity (which the authors partially relate the group differences to. Work recently emerged [O'Loinsigh et al, B Jrnl Pharmacology Dec 2000] which tentatively suggested that other non-MDMA amphetamines could augment MDMA associated 5HT depletions) and the contributions of co-use of other drugs upon cognition I'm referring here to memory work by authors such as Morgan, Gouzoulis-Mayfrank and Croft etc which are available in the Erowid/MAPS MDMA archive).

These confounds aside (although they are impossible to ignore), the statistical control used, because of the type of data collected, assumes that all subjects who reported using cannabis had used it to the same extent in the previous month, e.g. 1 joint per day is reported in the same way as 1/8th oz per day. I would argue that for studies such as these only quantitative drug use figures would be of any use for an ANCOVA control. Most importantly, ANCOVAs are not a substitute for randomized experimental design. Understandably though, it is impossible for any researcher to gain permission to perform repeated 'before and after' memory experiments involving administering Ecstasy.

In common with almost every community based survey/study of Ecstasy users, this experimental group indulged in other drugs more frequently than 'controls'. Data I have collected also makes me suggest that they used those other drugs in greater quantities as well. The study's drug use figures helpfully tell us that in the previous month Ecstasy users had used marijuana 25.1 times (vs 8.12 times in the control group), i.e they got stoned almost every day!

We may assume that this use is typical and takes place most months (unless specifically intended it is essential to capture stable and consistent drug using behaviors otherwise we may only be analyzing the effects of drug binges or atypical problematic use), so if the researchers are asking these subjects to remember how many times they forgot to do things in the past we may be not be allowing the participants to distinguish between times they were under the influence of cannabis (and other drugs) and times when they were not. No specific instruction is given to the subject to refer to drug free times in the Prospective Memory Questionnaire (and indeed would be strictly very difficult if these subjects are using drugs most day) so these deficits in memory may simply be due to the acute or sub acute effects of cannabis (which I believe affects the acquisition of memory) and not the effects of chronic MDMA use.

Forgetting why you have entered a room or what you were saying mid sentence are, I am told, frequent effects of heavy cannabis intoxication and are nor regarded as problematic. Additionally,were these subjects under the acute effects of cannabis when they completed the tests, without urinalysis we simply do not know? My own experience tells me (and Dr Karl Jansen mentions it in his chapter for inclusion in Dr Julie Holland's MDMA book) that even if study participants are asked to refrain from drug use many will not and some will not declare it if they have. Furthermore a group that has used Ecstasy a mean of 13.1 times in the previous month probably uses the drug every weekend. Lets hope that all these subjects were not tested in the few days after using the drug at a club. Prof Curran at UCL identified the well known 'mid-week' low after Ecstasy use and characterized it by depressed mood and cognitive dysfunction.

In summary I think that this work is extremely important in telling us that heavy regular recreational drug use, especially 'hangover' and acute and sub acute drug effects, may affect memory and self reporting of memory function. What the implications are for day to day functioning is unknown but many drugs education packages warn of the deleterious effects that use of any drug may have on school work and some occupational performance. I don't think these facts are in much doubt. Unfortunately for the UK media these were the headlines and research of the 1960s and 1970s. In my opinion, the methods used in this research do not tell us anything about the effects of Ecstasy use per se. Regular drug use by young people could certainly have "dire consequences" for them (prison for a start) but so too could continually reading that they have brain damage "similar to that seen in Alzheimer's" when they have not. Furthermore with maintained focus upon the effects of Ecstasy, which is by no means the only drug associated with the dancefloor, are we not also giving out the message that 'as long as you stay away from E, you'll be fine'? This approach ignores the possible harmful consequences of use of other dance drugs which are used by far more people in the UK than Ecstasy and are all associated with problems themselves and suggests that the only effects that we should be concerned about when discussing these drugs are those that have detrimental economic consequences, i.e work productivity will fall. Finally, does this artificial focus on Ecstasy and the identification of the elusive 'Ecstasy user' (who does not exist) not also indicate the fashions of scientific research which closely follow the whims of drug trends?

Harry Sumnall
Dept Psychology
University of Liverpool