In Reply: No Evidence of Decrease in Cognitive Function in Users of Low-Dose Ecstasy

Arch Gen Psychi 65(2): 236-237

In reply,

Krebs and Johansen raise some questions concerning the conclusions of our article “Cognition in Novice Ecstasy Users With Minimal Exposure to Other Drugs.”1 We interpret the absence of a retest effect on a verbal memory task in Ecstasy users as a decrease in verbal memory. This is based on the fact that the Ecstasy-naive subjects showed an increase in performance between the initial and follow-up examinations, while the Ecstasy users did not. The memory performance in our control group increased, with 4 words on total immediate recall and more than half a word on delayed recall at the second measurement occasion. However, Krebs and Johansen state that retest effects disappear within 1 month, a statement based on a review of Hawkins et al.2 In this review, 1 study is mentioned, in which no significant practice effects were seen in 30 normal subjects who were retested with a parallel version after 1 month.3 Another reviewed study in 19 undergraduates did find retest effects with a parallel form after 2 to 13 days.4 We find these 2 small studies meager evidence to conclude that retest effects cannot exist after 1 month. There are other studies that do show retest effects after more than 1 month.5-8 For example, 1 study in 38 healthy subjects reported an increase of 2.8 words on immediate recall and 0.8 word on delayed recall after an interval of 4 months.7 Perhaps the most compelling evidence that retest effects are the norm comes from a population-based study in 776 subjects that shows an increase of 4 words on immediate recall and 1 word on delayed recall after an interval of 3 years.8 (Moreover, most of the tests we used showed retest effects at follow-up [Table 2 of our article1]). The absence of improved performance in the Ecstasy-using group does not imply that Ecstasy users lack a practice effect. They probably also gained “test wiseness” and knew what they could expect. However, our hypothetic conclusion is that this practice effect could not fully compensate for the decreased memory functioning due to the Ecstasy use.

Krebs and Johansen correctly remark that a dose as high as 30 tablets of Ecstasy could not generally be called “low.” Therefore, we repeated the analyses after excluding 4 subjects who used 30, 20, 20, and 11 tablets, respectively. Fifty-four were kept in the analyses (range, 0.5-6 tablets; median, 1.5; mean, 1.95). This did not really change the results (Rey Auditory Verbal Learning Test [RAVLT] immediate recall, F1,104 = 4.92; P = .03; RAVLT recognition, odds ratio, 4.93; Wald {chi}21 = 4.44; P = .04; RAVLT delayed recall, F1,104 = 3.47; P = .06). (After including 1 subject who took 11 tablets, values for delayed recall were F1,105 = 4.17 and P = .04).

As Krebs and Johansen said, the average dose per use could be of significance. In our study, 60% of the subjects took a maximum of 0.5 to 1 tablet per use, 35% took 1.5 to 2 tablets per use, 2 subjects took 3 pills at 1 occasion, and only 1 subject took once a maximum of 4 pills. We do not know with certainty what the exact percentage of MDMA in the tablets was. However, the annual report of the Drug and Information Monitoring System shows that in the Netherlands in 2003 the mean concentration of MDMA in an Ecstasy tablet was 78 mg, with 95% to 97% of the Ecstasy tablets containing a maximum of 140 mg of MDMA; 83% to 87%, a maximum of 105 mg; and 45%, less than 70 mg.9-10 If we repeat the analyses without the 3 subjects who took more than 2 pills at 1 occasion, results remain significant for all 3 verbal memory measures. All considered, we do not think that average dose per use played a major role in our study.

Krebs and Johansen raise an important matter about potential negative consequences of anxiety to perform worse in Ecstasy users (“stereotype threat”). Because of ethical reasons, subjects were informed in advance about possible harmful effects of Ecstasy on the serotonin system, involved in mood, impulsivity, memory, and attention. Nonetheless, it remains remarkable that differences were found in verbal memory only, not in mood, impulsivity,11 visual memory, or attention.

We agree that it is important to distinguish between recreational Ecstasy use and controlled therapeutic use of MDMA. A balanced risk-benefit analysis should be made, as this is always important in prescribing or using medications, and potential candidates for therapeutic use should be adequately informed about all effects of the substance they take.


Correspondence: Ms Schilt, Amsterdam Institute for Addiction Research (AIAR), Department of Psychiatry, Academic Medical Center, PB 0.429, University of Amsterdam, PO Box 75867, 1070 AW Amsterdam, The Netherlands Thelma Schilt

Financial Disclosure: None reported.

Thelma Schilt, MSc; Maartje M. de Win, MD, PhD; Maarten Koeter, PhD; Gerry Jager, PhD; Dirk J. Korf, PhD; Wim van den Brink, MD, PhD; Ben Schmand, PhD

  1. Schilt T, de Win MM, Koeter M, Jager G, Korf DJ, van den Brink W, Schmand B. Cognition in novice ecstasy users with minimal exposure to other drugs: a prospective cohort study. Arch Gen Psychiatry. 2007;64(6):728-736.
  2. Hawkins KA, Dean D, Pearlson GD. Alternative forms of the Rey Auditory Verbal Learning Test: a review. Behav Neurol. 2004;15(3-4):99-107.
  3. Crawford JR, Stewart LE, Moore JW. Demonstration of savings on the AVLT and development of a parallel form. J Clin Exp Neuropsychol. 1989;11(6):975-981.
  4. Shapiro DM, Harrison DW. Alternate forms of the AVLT: a procedure and test of form equivalency. Arch Clin Neuropsychol. 1990;5(4):405-410.
  5. Uchiyama CL, D’Elia LF, Dellinger AM, Becker JT, Selnes OA, Wesch JE, Chen BB, Satz P, van Gorp W, Miller EN. Alternate forms of the Auditory-Verbal Learning Test: issues of test comparability, longitudinal reliability, and moderating demographic variables. Arch Clin Neuropsychol. 1995;10(2):133-145.
  6. Valentijn SA, Van Boxtel MP, van Hooren SA, Bosma H, Beckers HJ, Ponds RW, Jolles J. Change in sensory functioning predicts change in cognitive functioning: results from a 6-year follow-up in the maastricht aging study. J Am Geriatr Soc. 2005;53(3):374-380.
  7. Valentijn SA, van Hooren SA, Bosma H, Touw DM, Jolles J, van Boxtel MP, Ponds RW. The effect of two types of memory training on subjective and objective memory performance in healthy individuals aged 55 years and older: a randomized controlled trial. Patient Educ Couns. 2005;57(1):106-114.
  8. Van der Elst W, Van Boxtel MP, Van Breukelen GJ, Jolles J. Detecting the significance of changes in performance on the Stroop Color-Word Test, Rey’s Verbal Learning Test, and the Letter Digit Substitution Test: the regression-based change approach. J Int Neuropsychol Soc. 2008;14(1):71-80.
  9. Drugs Informatie en Monitoring System. Jaarbericht 2003. Utrecht, The Netherlands: DIMS/Trimbosinstituut; 2003.
  10. Drugs Informatie en Monitoring System. Jaarbericht 2004. Utrecht, The Netherlands: DIMS/Trimbosinstituut; 2004.
  11. de Win MM, Schilt T, Reneman L, Vervaeke H, Jager G, Dijkink S, Booij J, van den Brink W. Ecstasy use and self-reported depression, impulsivity, and sensation seeking: a prospective cohort study. J Psychopharmacol. 2006;20(2):226-235.

Arch Gen Psychiatry. 2008;65(2):236-237.

Read Krebs and Johansen’s letter concerning the Schilt et al. study.