Neuroimaging in Human MDMA (Ecstasy) Users

Millions of people worldwide have used MDMA recreationally, though the purity of Ecstasy sold as MDMA is uncertain. MDMA is a public health concern not because it commonly causes dependence, but because animal studies show it can produce long-lasting reductions in brain serotonin markers, particularly in fine-diameter axons from the dorsal raphe nucleus. Neuropsychological, neuroendocrine, and neuroimaging studies in human users suggest long-lasting brain function changes consistent with serotonin toxicity. A cortical model based on animal data helps design and interpret neuroimaging studies, but findings are controversial and often unreplicated across laboratories and modalities. This paper reviews existing evidence and proposes future research directions.

Study at a glance

Abstract

MDMA (3,4 methylenedioxymethamphetamine) has been used by millions of people worldwide as a recreational drug. The terms “MDMA” and “Ecstasy” are often used synonymously, but it is important to note that the purity of Ecstasy sold as MDMA is not certain. MDMA use is of public health concern, not so much because MDMA produces a common or severe dependence syndrome, but rather because rodent and nonhuman primate studies have indicated that MDMA (when administered at certain dosages and intervals) can cause long‐lasting reductions in markers of brain serotonin (5‐HT) that appear specific to fine‐diameter axons arising largely from the dorsal raphe nucleus (DR). Given the popularity of MDMA, the potential for the drug to produce long‐lasting or permanent 5‐HT axon damage or loss, and the widespread role of 5‐HT function in the brain, there is a great need for a better understanding of brain function in human users of this drug. To this end, neuropsychological, neuroendocrine, and neuroimaging studies have all suggested that human MDMA users may have long‐lasting changes in brain function consistent with 5‐HT toxicity. Data from animal models leads to testable hypotheses regarding MDMA's effects on the human brain. Because neuropsychological and neuroimaging findings have focused on the neocortex, a cortical model is developed to provide a context for designing and interpreting neuroimaging studies in MDMA users. Aspects of the model are supported by the available neuroimaging data, but there are controversial findings in some areas and most findings have not been replicated across different laboratories and using different modalities. This paper reviews existing findings in the context of a cortical model and suggests directions for future research.