Department of Neuropsychology & Psychopharmacology
Cortisol levels and MDMA-induced memory impairment Kuypers, K.P.C. & Ramaekers, J. G. Department of Neuropsychology & Psychopharmacology, Faculty of Psychology & Neuroscience, Maastricht University,The Netherlands
Background Ecstasy use is commonly linked with memory deficits in abstinent ecstasy users. Similar impairments are being found during ecstasy intoxication after single doses of MDMA [1]. The concordance of memory impairments during intoxication and abstinence suggests a similar neuropharmacological mechanism underlying acute and chronic memory impairments in ecstasy users. The mechanism underlying this impairment is to date not known. Hypothesis Aim Cortisol might play an important role in this mechanism as cortisol, To block the MDMA-induced acute memory defect by giving implicated in the regulation of memory performance [2], can be participants a cortisol synthesis inhibitor (Metyrapone®) together brought out of balance by stressors like MDMA [3]. with a single dose of MDMA.
Methods Subjects Design Test: 30- Word Learning Test (WLT) - 17 Polydrug MDMA users - Placebo-controlled, within subject -30 Dutch words; 3 learning trials -6Ƃ; 11 ƃ - 4 treatment conditions - Dependent Variables: - Lifetime ecstasy use 1. Placebo = Placebo (9.30AM) + Placebo (10.30AM) -Immediate Recall (IR) - 15 Ss 20 times 2. Metyrapone = Metyrapone (750mg) + Placebo -Delayed Recall (DR): after 30’ delay - 2 Ss 85-120 times 3. MDMA = Placebo + MDMA (75mg) Cortisol assessments: Blood samples: 1h [4] - IQverbal 4. Metyrapone + MDMA and 1.5h after respectively pretreatment -110.29 ± 4.043 (range: 105-117) & treatment
Time (AM) 9:00 9:30 9:35-10:25 10:25 10:30 10:35-11:55 11:55 12:00-13:15 Activity
Figure 1. Schematic representation of a test day
Results
Placebo Metyrapone MDMA Metyrapone+ MDMA Placebo Metyrapone MDMA Metyrapone + MDMA 1600
30 1000 1400 3 3 900 3 1200 800 3 700 1000 3 20 1 600 1 3 800 3 1 3 4 3 3 3 500 3 31 3 600 2 3 2
(nmol/l) 400 1 1 1 1 10 300 4 1 1 2 400 1 4 4 4 1 1 200 4 4 41 2 4 4 14 2 1 200 24 42 2 12 100 2 42 4 2 2 2 2 2 Cortisol Concentration in Blood (nmol/l) 2 Correct Recalled Words (Number) 0 Cortisol Concentration in Blood 0 0 IR 1 IR 2 IR 3 DR 10:25 11:55 0 10 20 30 40 50 60 70 80 IR Total (Number) Trial Time (AM) Figure 2. 30-WLT. After MDMA Figure 3. Cortisol concentrations in blood, Figure 4. Absence of a significant treatment, Ss recalled less words during (1h &) 1.5h after (pre)-treatment. correlation between total number of immediate (7.7) and delayed (3.5) recall Concentrations were significantly lower correct recalled words of the WLT and compared to placebo. after Metyrapone treatment, and higher cortisol concentrations in blood (at the after MDMA treatment, compared to moment of WLT). placebo. The MDMA-effect was absent when Ss were pretreated with Metyrapone.
Conclusion Main findings indicated that whereas pretreatment with Metyrapone blocked the expected MDMA-induced increase in cortisol levels in blood, it did not prevent the MDMA-induced memory deficit from happening. We therefore conclude that MDMA-induced increases in cortisol concentrations are not responsible for impairing memory performance while intoxicated with MDMA.
References [1] Kuypers, K. P. C., Ramaekers, J. G., 2005 Transient memory impairment after acute dose of 75mg 3.4-Methylene-dioxymethamphetamine. Journal of Psychopharmacology 19, 633-639. [2] Erickson, K., Drevets, W., Schulkin, J., 2003 Glucocorticoid regulation of diverse cognitive functions in normal and pathological emotional states. Neuroscience and Biobehavioral Reviews 27, 233-246. [3] Lamers, C. T., Ramaekers, J. G., Muntjewerff, N. D., Sikkema, K. L., Samyn, N., Read, N. L., Brookhuis, K. A., Riedel, W. J., 2003 Dissociable effects of a single dose of ecstasy (MDMA) on psychomotor skills and attentional performance. Journal of Psychopharmacology 17, 379-387. [4] Schmand, B., Bakker, D., Saan, R., & Louman, J. (1991). De Nederlandse Leestest voor Volwassenen: een maat voor het premorbide intelligentieniveau. Tijdschrift voor Gerontologie en Geriatrie, 22, 15-19.
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This study was supported by an Open Competition Grant (no.400-07-213) from the Netherlands Organisation for Scientific Research (NWO)