'Ecstasy' or 3,4-methylene-dioxy-meth-amphetamine (MDMA) is a psycho-stimulant drug of abuse. Upon consumption, it typically produces sensations of euphoria, increased sensory awareness, and facilitated social communication. However, repeated use of MDMA has been strongly linked with sleep disorders, depressed mood, memory impairment and elevation of anxiety, impulsiveness and hostility. Since several prescription drugs - chemically and operationally similar to the "banned" MDMA are considered "safe", the therapeutic use of MDMA has seemed a coherent idea to some. Further, the absence of concrete estimates of MDMA doses that are harmful to humans, and the variability in the nature, intensity and longevity of the impairments that they cause, have kept the debate on the use of MDMA open.
    MDMA operates primarily by affecting the serotonergic system of the brain, which is known to modulate mood, emotion, sleep and appetite. In general, high and low levels of the pivotal neuro-transmitter serotonin have been seen to correspond to positive and negative extremes of emotion respectively. Under normal conditions of stimulation, the serotonin released by the serotonin-producing nerve cells triggers responses in the adjacent neurons. A recycling process called re-uptake then ensues, which leads to the excess serotonin in the synapse being degraded or reabsorbed. MDMA alters the serotonin-mechanics by promoting the release and inhibiting the re-uptake of serotonin. Thus, a short-term serotonin overload results and causes the characteristic euphoric sensations. Brain-activity in the human limbic orbito-frontal and antero-temporal structures, which are known to be involved in emotional processes, has been empirically recorded following MDMA administration. Thus the spacio-temporal correlation between MDMA and its immediate emotional effects has sound biochemical and anatomical backings.
    Several experimental studies in animals have shown that this initial serotonin-overload is followed by a second phase : a long-lasting decrease in serotonin. This effect could result from a single large dose or from several moderate doses. It has been seen to last after abstinence from MDMA, for up to a year in rats and up to 7 years in non-human primates. Though the exact mechanism of this serotonin-depletion is unknown, a possible explanation may be obtained from the opponent process theory of motivation. As an "A-process" (MDMA consumption) lead to an increase in serotonin levels, a "B-process" was invoked that tried to counter this effect and maintain homeostasis. With repeated experience (habitual abuse), this "B-process" increased in magnitude. It thus removed the excess serotonin more efficiently, ultimately leading to sub-normal serotonin levels. It is this relatively permanent depletion of serotonin that is the putative cause of MDMA's long-term neuro-toxicity. Researchers have established that imbalances in the serotonergic system could cause obsessive compulsive disorder, sleep onset latency, aggressive behaviors, depression and suicidal tendencies. It is this chronic and non-ephemeral nature of the pathologies that has made most scientists take the cautious stand on MDMA usage.
    In summary, researchers have elucidated the biochemical pathways triggered by MDMA, and have also observed a correlation between the extent of "Ecstasy"-exposure and the severity of cognitive impairment. Further, histological analyses of brain-tissue from MDMA-administered subjects have revealed effects like loss of forebrain serotonergic axons and serotonin-system rewiring. Paradoxically, other amphetamines (Adderall) and chemicals that target the serotonergic system (Prozac), which could promote this brain-rewiring equally well, have always been deemed "safe" prescription drugs. Some scientists suggest that this neuron-rewiring may not be reflective of brain damage at all. Indeed, an increase of the glial fibrillary acidic protein in the brain, a reaction diagnostic of chemicals known to damage the brain, has not been observed for MDMA. In the light of such evidence, it has been suggested that MDMA administered in controlled doses could possibly alleviate depression-like syndromes by increasing serotonin levels. Thus, while the banning of MDMA to discourage its recreational use is justified, claiming that it causes permanent damage even in small doses is not. The therapeutic possibilities that MDMA has to offer definitely constitute a promising area that warrants more research.