Inhibition of MDMA-induced increase in cortisol does not prevent acute impairment of verbal memory

Kuypers, Kim PC; Torre Fornell, Rafael de la; Farré Albaladejo, Magí; Pujadas Bastardes, Mitona; Ramaekers, Johannes G.

doi:http://dx.doi.org/10.1111/j.1476-5381.2012.02196.x

Inhibition of MDMA-induced increase in cortisol does not prevent acute impairment of verbal memory

Citation

Kuypers KP, de la Torre R, Farre M, Pujadas M, Ramaekers JG. Inhibition of MDMA-induced increase in cortisol does not prevent acute impairment of verbal memory. British journal of pharmacology. 2013; 168(3): 607-617. DOI 10.1111/j.1476-5381.2012.02196.x

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.