Part of the Neuron Affected: Erin Misoni

The part of the brain that is most affected by MDMA are the serotonin-producing neurons. Through much animal research with MDMA it has been found that this drug significantly damages serotonin-producing neurons in the brain. Serotonin is a major neurotransmitter, or chemical messenger, in the brain that influences mood, appetite, sleep, and other important functions.

Once MDMA is taken into the body the initial effects produce heightened levels of serotonin in the brain. Following these discharges of serotonin, ongoing synthesis has shown to be inhibited. After 3 to 6 hours noticeable reductions in brain serotonin concentrations can be found. These initiatory effects appear to produce changes in serotonin that are luckily reversible (Cohen, 19). In the second stage (twenty-four hours to one week), the prolonged effects of MDMA become more apparent, with significant damage to serotonin nerve terminals characterized by substantial loss of serotonin reuptake sites. These degenerative effects on serotonergic neurons are known to be irreversible (Cohen, 20).

Studies have demonstrated that MDMA alters neurotransmitter functioning and causes drastic neurodegenerative effects on serotonergic function. Following treatment monoamine levels have been shown to be altered in a region-specific and dose-dependent manner. MDMA also causes neurodegeneration of serotonergic uptake sites, as well as marked reductions in the activity of tryplophan hydroxylase, the rate limiting enzyme of serotonin synthesis (Cohen, 20).

Studies have revealed that MDMA is neurotoxic to serotonergric nerve fibers in rats, mice, guinea pigs, and monkeys (Cohen, 20). Dr. George Ricaurte, a scientist at the Johns Hopkins Medical Institution found that 12 to 18 months after the brains of squirrel monkeys had been damaged by MDMA, serotonin-producing nerve fibers had regrown abnormally in some regions as well as failing to regrow at all others (Mathias, 1). "MDMA selectively damages serotonin neurons in virtually all species to date," Dr. Ricaurte says (Mathias, 1).

During the long-term study with the squirrel monkeys, some brain areas, those containing structures involved in memory and learning, damaged neurons failed to recover. However, in other brain areas, particularly those areas involved in regulating sleep and appetite, those damaged neurons regrew nerve fiber excessively, resulting in too much serotonin being released. "This means that when we evaluate humans previously exposed to high doses of MDMA, we should be looking for less of serotonin function in some regions, but perhaps normal or increased serotonin function in other regions," Dr. Ricaurte says (Mathias, 2).

Dr. Ricaurte's studies have found that MDMA damages serotonin-producing neurons in the brains of nonhuman primates. The illustration shows a normal neuron. The shaded area in the middle illustration shows the axon terminals of the neuron that are damaged by MDMA. The illustration on the right shows how, 12 to 18 months after being damaged by MDMA, serotonin-producing nerve fibers have regrown excessively in some areas and not at all in others (Mathias, 1).

A decade of research has shown MDMA causes a deficit of brain serotonin in every animal species, but what about in the human species? Just recently, several strands of evidence have indicated that similar deficits occur in people (Morris, 1). Some researchers whom wanted to investigate the status of brain 5-HT neurons in MDMA users conducted a experiment, and their results were surprising. Their findings are as followed: " In summary, our data suggest that people who use MDMA as a recreational drug are unwittingly putting themselves at risk of developing brain 5-HT neural injury. In addition, systematic studies of MDMA-exposed individuals with highly selective brain 5-HT transporter deficits may give important insights into the functional role of brain 5-HT in human behavior. Potential functional consequences of MDMA-induced brain 5-HT neurotoxic lesions are not yet clear, but may include depression, anxiety, memory disturbance, and other neuropsychiatric disorders in which brain 5-HT has been implicated"(McCann, 8). These findings prove that MDMA has the same effect on human serotonergic neurons as it does on animal's serotonergic neurons.

In some research MDMA not only proves to damage serotonergic neurons, but also to decrease the concentrations of cerebrospinal fluid 5-hydroxindoleacetic acid (5-HIAA) the primary serotonin metabolite. Significant decreases in concentrations of 5-HIAA have consistently been found in laboratory animals following the administration of the drug. One study found concentrations of 5-HIAA in human cerebrospinal fluid to be greatly reduced in individuals who have had prior exposure to MDMA (Morris, 5). However, a different study, did not find MDMA users to have decreased levels of 5-HIAA (McCann, 9).

To conclude, the long term use of MDMA causes some serious damage to the serotonin producing neurons of the brain. This long term use results in permanent damage to neurons in some areas of the brain (memory and learning), and the excessive regrowth of damaged neuron nerve fibers in other areas of the brain (sleep and appetite) (Mathias, 2). In the beginning various experiments on animals found this statement to be true, and as scientists have progressed in their research they have found that MDMA also affects the serotonergic neurons in humans (Morris, 1). Other research has suggested that MDMA decreases concentrations of cerebrospinal fluid 5-hydroxindoleacetric acid, but not enough research has been done to support this theory (Morris, 5).

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