The confounding problem of polydrug use in recreational ecstasy/MDMA users: a brief overview

The popular dance drug ecstasy (MDMA) is neurotoxic to central serotonergic neurons in laboratory animals and possibly in humans. Studies have reported alterations in serotonergic transmission and neuropsychiatric abnormalities in ecstasy users that may relate to MDMA-induced neurotoxic brain damage. The most consistent findings associate subtle cognitive, particularly memory, deficits with heavy ecstasy use. However, most studies have important methodological problems, especially the widespread pattern of polydrug use—commonly alcohol, cannabis, and stimulants (amphetamines and cocaine)—which makes it difficult to link findings to MDMA alone. Stimulants are also neurotoxic and may act synergistically with MDMA, while cannabis has complex interactions, including neuroprotective actions that can partially block MDMA-induced neurotoxicity in animals. Future longitudinal research should clarify these relationships.

Study at a glance

Abstract

The popular dance drug ecstasy (3,4-methylenedioxymethamphetamine -- MDMA) is neurotoxic upon central serotonergic neurons in laboratory animals and possibly also in humans. In recent years, several studies reported alterations of serotonergic transmission and neuropsychiatric abnormalities in ecstasy users which might be related to MDMA-induced neurotoxic brain damage. To date, the most consistent .ndings associate subtle cognitive, particularly memory, de.cits with heavy ecstasy use. However, most studies have important inherent methodological problems. One of the most serious confounds is the widespread pattern of polydrug use which makes it dif.cult to relate the .ndings in user populations to one speci.c drug. The present paper represents a brief overview on this issue. The most commonly co-used substances are alcohol, cannabis and stimulants (amphetamines and cocaine). Stimulants are also neurotoxic upon both serotonergic and dopaminergic neurons. Hence, they may act synergistically with MDMA and enhance its long-term adverse effects. The interactions between MDMA and cannabis use may be more complex: cannabis use is a wellrecognized risk factor for neuropsychiatric disorders and it was shown to contribute to psychological problems and cognitive failures in ecstasy users. However, at the cellular level, cannabinoids have neuroprotective actions and they were shown to (partially) block MDMA-induced neurotoxicity in laboratory animals. In future, longitudinal and prospective research designs should hopefully lead to a better understanding of the relation between drug use and subclinical psychological symptoms or neurocognitive failures and, also, of questions around interactions between the various substances of abuse.