IS MDMA REALLY NEUROTOXIC?

IS MDMA REALLY NEUROTOXIC?

There is still controversy about whether MDMA causes long-term dam­age to serotonin neurons, a concern that arose from previous experience with similar amphetamine-like serotonin-releasing drugs. Other drugs that release both dopamine and serotonin ⁽methamphetamine, for exam­ple) have been shown in laboratory studies to cause long-lasting changes in either (or both) dopamine or serotonin neurons in the brain. None of the usual contents of the ends of the serotonin neurons that normally release serotonin onto the neuron's receptors (nerve terminals) can be detected. The serotonin itself, the serotonin transporter, and other com­ponents of the terminal are decreased markedly. With almost all of these drugs, the amount of damage is dose- and time-related. Small doses pro­duce little or no damage; moderate doses produce marked decreases in

serotonin indices but leave the serotonin system still functional; and

large doses can eliminate the ability of these neurons to release serotonin for months.

MDIVIA acts like other drugs in the same class. In experimental studies in rats and primates, MDMA produced temporary loss of serotonin,which doesn't present any real long-term problem but may be responsible for the midweek blues. It also produces the same kind of long-term changes that the other amphetamine-like drugs produce. With some dose regimens, a limited amount of recovery occurred, while with higher dose regimens, no recovery occurred. One of the controversies about MDMA is whether the loss of these markers really means that the nerve endings are gone or just depleted of their contents. None of the studies conducted so far provide incontrovertible proof that the nerve endings are gone or not. However, there is little question that at the very least, the serotonin itself, the transporter, and the main synthetic enzyme are reduced to very low levels for a long time after repeated, heavy exposure to MDMA. In any case, the serotonin neuron is not capable of functioning normally, and so it may be a moot point if the terminal is there and devoid of con­tents or actually gone. How much MDMA is necessary to produce signifi­cant long-term damage? The dose range that produced permanent damage in experiments with squirrel monkeys was about the equivalent of a 150- pound person taking 350 milligrams spaced over four days. Earlier stud­ies showed that this occurred when the drug was administered by injection in the monkeys, but more recent studies using oral administra­tion, resembling the way that humans take the drug, report similar results. An average human dose of Ecstasy is about 100 milligrams.

Does the same type of damage happen in people who take high doses of MDMA for a long time? An increasing number of studies suggest that the answer is yes. Numerous studies show that levels of major serotonin

markers like the serotonin transporter or the main metabolite of sero‑

tonin in the nervous system are suppressed in Ecstasy users. None of

these studies is perfect anti the debate continues, but the evidence is

mounting that long-term decreases in serotonin neuron function occur in

heavy MDMA users (people who use a hundred times or more over sev‑

eral years). We don't know if these effects reverse if someone stops using

MDMA, although some studies indicate that this might be so.

What are the long-term effects of this type of serotonin loss? Are some of the anxiety and learning disorders that we discussed caused by this type of damage? Residual anxiety and irritability/hostility have been reported in a number of heavy Ecstasy users. Because increased levels of serotonin have been associated with improved mood (see the "Hallucino­gens" chapter), and its loss with depression in some cases, it is not unrea­sonable to speculate that mood disorders might be in the future for heavy

Ecstasy users.