Enantio-selective cognitive and brain activation effects of N-ethyl-3,4-methylenedioxyamphetamine in humans

Introduction

With the advent of cognitive neuroscience and functional brain imaging, substituted amphetamine derivatives such as MDMA and the closely related N-ethyl-3,4-methylenedioxyamphetamine (MDE) can be studied in humans with a combination of subjective, neuropsychological and brain-imaging measures. Earlier research indicated that these agents produce entactogenic subjective effects (changes in affect, perception and cognitive style) and act on serotonergic and catecholaminergic systems. Animal work has shown enantiomer-specific effects for MDE, with behavioural differences between the (R)- and (S)-forms, but human data on stereoselective effects were lacking. Spitzer and colleagues set out to characterise the enantio-selective effects of (R)-MDE and (S)-MDE in healthy volunteers. The study aimed to compare subjective experience, neuropsychological performance and functional MRI activation during low-level visual and higher-level semantic tasks after a single oral dose of each enantiomer, using a randomised double-blind crossover design. The investigators hypothesised that the two enantiomers would produce dissociable effects on mood, cognition and regional brain activation, reflecting differential actions on serotonergic and dopaminergic systems and on cortical areas such as primary visual cortex and frontal regions.