The Neuropsychopharmacology and Toxicology of 3,4‐methylenedioxy‐N‐ethyl‐amphetamine (MDEA)

MDEA, also known as "eve," is a ring-substituted amphetamine chemically and pharmacologically similar to MDMA. It produces psychomotor stimulation, mild perceptual changes, feelings of closeness, positive emotional states, and sympathomimetic physical effects. The term "ecstasy" now refers to a group of nearly identical compounds including MDA, MDMA, MDEA, and MBDB, and many pills contain mixtures. This review describes MDEA-specific pharmacodynamics and kinetics from animal and human challenge studies, and presents case reports of fatalities with toxicologically confirmed MDEA. Evidence for serotonergic neurotoxicity comes only from animal studies; human risk is unclear because users consume impure substances. Future animal studies using human-like dosing patterns and directly comparing individual ring-substituted amphetamines are needed to resolve controversies about neurotoxicity and its functional consequences.

Study at a glance

Abstract

ABSTRACT This paper reviews the pharmacology and toxicology of 3,4‐methylenedioxy‐N‐ethyl‐amphetamine (MDEA, “eve”). MDEA is a ring‐substituted amphetamine (RSA) like MDMA, its well known N‐methyl analog. Both have become very popular substances of abuse in the techno‐ and house‐music scene. They can evoke psychomotor stimulation, mild alterations of perception, sensations of closeness and a positive emotional state as well as sympathomimetic physical effects. At present, the name “ecstasy” is no longer used only for MDMA, but for the whole group of RSAs (MDA, MDMA, MDEA and MBDB) as they are chemically and pharmacologically nearly identical; moreover, many ecstasy pills contain mixtures of the RSAs. Hence, for a selective review on MDEA, it is crucial to strictly differentiate between: 1) street and chemical names, and 2) studies with or without chemically defined substances. In order to present MDEA‐specific information, the pharmacodynamics and kinetics are described on the basis of MDEA challenge studies in animals and humans. In the toxicology section, we present a collection of case reports on fatalities where MDEA was toxicologically confirmed. On the question of serotonergic neurotoxicity and possible long‐term consequences, however, MDEA‐specific information is available from animal studies only. The neurotoxic potential of MDEA in humans is difficult to estimate, as ecstasy users do not consume pure substances. For future research, challenge studies in animals using dosing regimens adapted to human consumption patterns are needed. Such challenge studies should directly compare individual RSAs. They will represent the most viable and fruitful approach to the resolution of the highly controversial issues of serotonergic neurotoxicity and its functional consequences.