MDMA’s Effects on the Brain

MDMA affects the brain by increasing the activity of at least three neurotransmitters (the chemical messengers of brain cells): serotonin, dopamine, and norepinephrine. Like other amphetamines, MDMA enhances release of these neurotransmitters and/or blocks their reuptake, resulting in increased neurotransmitter levels within the synaptic cleft (the space between the neurons at a synapse).

MDMA causes greater release of serotonin and norepinephrine than of dopamine. Serotonin is a neurotransmitter that plays an important role in the regulation of mood, sleep, pain, appetite, and other behaviors. The excess release of serotonin by MDMA likely causes the mood-elevating effects people experience.

However, by releasing large amounts of serotonin, MDMA causes the brain to become significantly depleted of this important neurotransmitter, contributing to the negative psychological after-effects that people may experience for several days after taking MDMA.

Research in rodents and primates has shown that moderate to high doses of MDMA, given twice daily for four days, damages nerve cells that contain serotonin. MDMA-exposed primates showed reduced numbers of serotonergic neurons 7 years later, indicating that some of MDMA’s effect on the brain can be long-lasting.

Low serotonin is associated with poor memory and depressed mood, thus these findings are consistent with studies in humans that have shown that some people who use MDMA regularly experience confusion, depression, anxiety, paranoia, and impairment of memory and attention. In addition, MDMA’s effects on norepinephrine contribute to the cognitive impairment, emotional excitation, and euphoria that accompanies MDMA use.

Positron emission tomography (PET) brain imaging studies of people who have stopped using MDMA have shown decreases in brain activity at rest in multiple regions of the brain, including those involved in learning, memory, emotion formation and processing, and sensory and motor function.

Limitations of Current Research

Few imaging studies have explored the effects of moderate MDMA use on the human brain, and results that do exist are inconsistent due to methodological differences across studies. More studies are needed to determine whether the observed changes in brain activity in people who use MDMA are caused by MDMA, other drug use, or other common risk factors that predispose people to use MDMA.

Additionally, most studies in people do not have behavioral measures from before MDMA use started, making it difficult to rule out pre-existing differences or common underlying risk factors across groups that are separate from MDMA use. Factors such as gender, dosage, frequency and intensity of use, age at which use began, and the use of other drugs, as well as genetic and environmental factors all may play a role in some of the cognitive deficits associated with MDMA use and should be taken into consideration when studying the effects of MDMA in humans.