Abstract
Ecstasy/3,4-methylenedioxymethamphetamine (MDMA) use is proposed to cause damage to serotonergic (5-HT) axons in humans. Therefore, users should show deficits in cognitive processes that rely on serotonin-rich, prefrontal areas of the brain. However, there is inconsistency in findings to support this hypothesis. The aim of the current study was to examine deficits in executive functioning in ecstasy users compared with controls using meta-analysis. We identified k = 39 studies, contributing 89 effect sizes, investigating executive functioning in ecstasy users and polydrug-using controls. We compared function-specific task performance in 1221 current ecstasy users and 1242 drug-using controls, from tasks tapping the executive functions - updating, switching, inhibition and access to long-term memory. The significant main effect demonstrated overall executive dysfunction in ecstasy users [standardized mean difference (SMD) = -0.18, 95% confidence interval (CI) -0.26 to -0.11, Z = 5.05, p < 0.001, I 2 = 82%], with a significant subgroup effect (χ 2 = 22.06, degrees of freedom = 3, p < 0.001, I 2 = 86.4%) demonstrating differential effects across executive functions. Ecstasy users showed significant performance deficits in access (SMD = -0.33, 95% CI -0.46 to -0.19, Z = 4.72, p < 0.001, I 2 = 74%), switching (SMD = -0.19, 95% CI -0.36 to -0.02, Z = 2.16, p < 0.05, I 2 = 85%) and updating (SMD = -0.26, 95% CI -0.37 to -0.15, Z = 4.49, p < 0.001, I 2 = 82%). No differences were observed in inhibitory control. We conclude that this is the most comprehensive analysis of executive function in ecstasy users to date and provides a behavioural correlate of potential serotonergic neurotoxicity.
Highlights
Ecstasy (3,4-methylenedioxymethamphetamine; MDMA) remains popular despite reports of potential long-term negative consequences associated with repeated use
Excluded papers at this stage included: review articles (23); acute administration studies (26); studies that were conducted using other substances/ did not involve ecstasy users (75); studies that were not experimental/did not include behavioural data/assess cognition (232); case studies (8); studies conducted in non-human samples (4); a study not written in English (1); and reanalyses of data (2)
Meta-regression using estimated lifetime dose of ecstasy to predict effect size of between-group differences was non-significant. This suggests that lifetime dose is not the greatest predictor in magnitude of Executive functions (EFs) deficit
Summary
Ecstasy (3,4-methylenedioxymethamphetamine; MDMA) remains popular despite reports of potential long-term negative consequences associated with repeated use (see Parrott, 2013a, b). A recent review by Murphy et al (2009) suggests that ecstasy-related cognitive dysfunction is not consistently reported in the literature, monitoring of research is necessary to gain a coherent understanding of drug effects. Executive functions (EFs) have been defined as a set of general-purpose control processes, required for regulating thought and action (Miyake & Friedman, 2012). The central executive is an integral component of working memory (Baddeley, 2000) and is required for coordinating and processing information. Some of the apparent inconsistency in the literature may be attributable to several of the classic working memory/‘executive’ tasks requiring use of multiple EFs: a problem of task impurity (Miyake & Friedman, 2012).
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