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Inhibition ofMDMA‐induced increase in cortisol does not prevent acute impairment of verbal memory

Kim P. C. Kuypers, Rafael de la Torre, Magı́ Farré, Mitona Pujadas, Jg Ramaekers

British Journal of Pharmacology September 4, 2012 DOI: 10.1111/j.1476-5381.2012.02196.x via OpenAlex

Summary

MDMA acutely impairs memory, but this effect is not caused by the rise in cortisol that MDMA also triggers. In a placebo-controlled, within-subject experiment with 17 polydrug MDMA users, blocking the cortisol increase with metyrapone (a cortisol synthesis inhibitor) did not prevent the memory deficit produced by a 75 mg dose of MDMA. Memory was tested at peak drug concentrations. The finding suggests that the neuropharmacological mechanism behind MDMA-induced memory impairment is independent of cortisol.

Study at a glance

Characteristics Placebo-controlled within-subject study Peer reviewed
Sample size 17
Population Polydrug MDMA users
Interventions MDMA Metyrapone
Dose 75 mg MDMA, 750 mg metyrapone
Topics MDMA
Keywords Memory impairment Neuroscience Psychology Medicine
Citations 23
Key finding Blocking MDMA-induced cortisol increases with metyrapone did not prevent MDMA-induced memory impairment, indicating cortisol is not responsible for the memory deficit.

Abstract

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 ± 3,4 metylenedioxymethamphetamine (MDMA). The concordance of memory impairments during intoxication and abstinence suggests a similar neuropharmacological mechanism underlying acute and chronic memory impairments. The mechanism underlying this impairment is to date not known. We hypothesized that cortisol might play an important role in this mechanism as cortisol, implicated in the regulation of memory performance, can be brought out of balance by stressors like MDMA. METHODS: In the present study, we aimed to block the MDMA-induced acute memory defect by giving participants a cortisol synthesis inhibitor (metyrapone) together with a single dose of MDMA. Seventeen polydrug MDMA users entered this placebo-controlled within subject study with four treatment conditions. The treatments consisted of MDMA (75 mg) and metyrapone (750 mg), alone and in combination, and double placebo. Pre-treatment with metyrapone or Placebo occurred 1 h prior to MDMA or Placebo administration. Memory performance was tested at peak drug concentrations by means of several memory tests. Cortisol levels were determined in blood and oral fluid; this served as a control measure to see whether manipulations were effective. RESULTS: Main findings indicated that whereas treatment with metyrapone blocked the expected MDMA-induced increase in cortisol levels in blood, it did not prevent the MDMA-induced memory deficit from happening. CONCLUSION: We therefore conclude that MDMA-induced increments in cortisol concentrations are not related to MDMA-induced memory impairments.

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