“Drug find could give ravers the jitters”.
Science. 2002;297:2185, 2187.
'Ecstasy' is a cruel misnomer for the party drug (±)3,4-methylenedioxymethamphetamine (MDMA). Long known to disrupt neurons that communicate via the neurotransmitter serotonin, the controversial drug now appears to have even more potential for roughing up the dopamine system.
A quintessential social drug, ecstasy heightens sensations, gives a euphoric rush, and creates feelings of warmth and empathy. It ostensibly achieves this effect by causing neurons to spurt huge quantities of serotonin. In the immediate aftermath, the partier is temporarily drained of serotonin, often depressed and unable to concentrate. Some researchers see strong evidence from both brain and behavioral research that permanent brain damage also can result from MDMA use, but others are skeptical and suggest that the drug might be useful for certain types of psychotherapy.
Now George Ricaurte and colleagues at Johns Hopkins University School of Medicine in Baltimore report on page 2260 that ecstasy can cause 'profound dopaminergic toxicity,' possibly explaining some of the drug’s reported negative short- and longterm effects. Researchers administered the equivalent of a heavy party night’s worth of MDMA to monkeys. The damage they observed suggests that one all-night 'rave' might be enough to induce permanent brain damage and make a person more vulnerable to Parkinson’s disease, which is caused by a loss of dopamine-producing neurons.
The researchers injected three doses of MDMA into five monkeys over a period of 9 hours. One monkey died of hyperthermia within hours: Overheating is one of the main side effects of ecstasy. Another grew shaky after the second dose and was not given the third. After 2 weeks, the three other animals were killed and found to have lasting reductions in systems that process serotonin and, even more markedly, dopamine. These neurotransmitters were depleted, and neurons that use them showed damage to their axons, projections that send signals to other cells. The two-dose monkey, killed after 6 weeks, showed similar symptoms. The researchers repeated the regimen with five baboons and, even 8 weeks after exposure, recorded a 'profound loss' of markers seen in healthy dopaminergic axons.
Ricaurte says that other studies might have missed such dopamine system damage because they spaced the doses farther apart; protracted MDMA exposure, in contrast, might make dopamine neurons more vulnerable to the drug’s toxic effects. The researchers go on to speculate that damage to the dopamine system might be responsible for cognitive deficits, such as memory loss, seen in some MDMA users. They assert that one reason no one has associated MDMA with parkinsonism might be because the disease does not manifest itself until 70% to 80% of brain dopamine has been depleted. Andy Parrott, head of the Recreational Drugs Research Group at the University of East London, calls the findings 'very worrying.' He points out that some ecstasy takers-even 'novice' users- have motor symptoms such as tremors and twitches, 'which may be best explained in these dopaminergic terms,' because dopaminedependent neurons are one of the major lines of communication in the motor system. Other researchers are continuing to withhold judgment about the perils of MDMA, pointing to methodological difficulties in this kind of research and evidence that the damage might be only temporary.
Cognitive neuroscientist Jon Cole of the University of Liverpool, for example, is skeptical about the Parkinson's risk, so far 'there is only a single case report of parkinsonism related to the use of ecstasy. The sheer number of ecstasy users indicates that there would be millions of these patients presenting fortreatment.' Nonetheless, he says the study might call for a major revision of the existing view of MDMA: 'The entire human literature relies on the notion that MDMA is a selective serotonergic neurotoxin.
The Johns Hopkins finding is thus unlikely to put an end to the ongoing debate over MDMA. Criminalized in the United States in 1985, MDMA is still a subject of intense controversy, because some psychologists believe it can be a useful adjunct to psychotherapy—helping people open up emotionally, especially those suffering from posttraumatic stress disorder. Indeed, trials are ongoing in Israel and Spain, and the U.S. Food and Drug Administration approved a new one last November to be conducted in North Carolina.