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What happens next is less clear. According to Dr. George Ricaurte, a neurotoxicologist at Johns Hopkins University School of Medicine, monkeys dosed with MDMA show evidence of "pruning"a rewiring of the brain's serotonin system in which longer axons are lost, replaced by a dense growth of shorter ones. This pruning phenomenon remained evident eight years later, and although there's no proof of permanent changes, that's also, says Ricaurte, "a pretty long time, given monkeys live 25 years."
Since these changes are associated with decreased serotonin levels and lower numbers of serotonin transporters, Ricaurte believes they indicate damage from Ecstasy. "It's a harmful drug, and it's harmful in doses used by humans," he says.
O'Callaghan thinks this view is too simplistic. He says that just because the drug affects serotonin doesn't mean the damage takes place in those neurons. The rewiring, he argues, stems from something other than injury. "The [pruning phenomenon] is not necessarily reflective of damage," he says, "just profound and long-lasting changes."
He contends that if MDMA caused nerve-cell degeneration, star-shaped cells would form, leading to an increase of the glial fibrillary acidic protein, or GFAP. "Any chemical known to damage the brain has caused an increase in GFAP," explains O'Callaghan. "We don't see that response with MDMA."
While detractors agree that GFAP is a valid indicator of brain damage, they still take issue with O'Callaghan's measurements. "MDMA is a potent brain neurotoxin. The entire field reads the literature as such," says Ricaurte. "Are all 100 nails in to shut the coffin? No. But are there 70, 85, 90? At what point do you look at the data and say it's met a certain criteria? That criteria's been met long ago."
O'Callaghan doesn't get invited to speak at many conferences anymoreeven though he has been publishing extensively in this area for years. So politicians end up listening less to dissidents like him than to mainstreamers like Ricaurte and Dr. Alan Leshner, director of the National Institute on Drug Abuse. In a hearing before the Senate Subcommittee on Governmental Affairs this past July, Leshner stated, "There is substantial evidence to show that MDMA damages brain cells. Within the scientific community we cannot say with absolute certainty how and to what extent...but there is across-the-board agreement that brain damage does occur."
But O'Callaghan believes the whole idea of neurotoxicityof brain damagehas been tossed around too freely. A single dose of reserpine, a prescription drug used to treat hypertension, markedly lowers serotonin levels for extended periods. "It's just as neurotoxic as MDMA, if you equate neurotoxicity with serotonin decrease," he says. "But if you look at damage as defined by loss of structure, you don't see it [with MDMA], even in whopping doses."
The long-term consequences of MDMA use are similarly ill-defined. "The evidence up to date has been pretty crummy," Dr. H. Valerie Curran, a psychopharmacology professor at University College London, told the NIDA conference in July, noting that the most consistent findings relate to learning and memory. "The effects are subtle, but have real implications."
If MDMA does indeed cause brain damage by pruning the neuronal pathways, then a whole host of serotonin agents, including Prozac and Adderall, could be rewiring, and thus damaging, our brains. The latteroften given to hyperactive childrenis particularly worrisome, say critics, because it also affects dopamine, which helps the immature brain develop normally.
A paper co-authored by O'Callaghan in Brain Research last year concluded that all compounds acting on the brain's serotonin system can cause changes in serotonin neurons. O'Callaghan says the creation of these abnormalities, including corkscrew-shaped neurons, could be part of Prozac's desired therapeutic effect.
While scientists like Ricaurte say Ecstasy is a much different drug from Prozac, it's not that different from the amphetamine Adderall. They admit that the research on such pharmaceuticals is still lacking. "I think we need more experimental studies addressing that question," says Ricaurte. "We know amphetamines can damage dopamine cells. What is not known is whether the amount of amphetamine used in kids is the amount required for toxicity."
This scares O'Callaghan. "You can market a compound," he says, "unless it puts holes in your head."
What separates a good drug from a bad drug? Why is it OK to prescribe amphetamines to children but bad when they ingest them for fun? Drug-company ads pitch chemical remedies for everything from social anxiety to severe PMS. Since 1970, their profits have more than quadrupled; roughly a quarter are from drugs that affect the central nervous system and sensory organs. More people are taking more pillswhether Ecstasy or Prozacto feel better. Yet the war on drugs drags on.
For Ecstasy, it began in the early '80s, when rising use and a "designer drug" media scare forced the Drug Enforcement Agency to take notice. Although a judge ruled during 1985 hearings that MDMA had therapeutic value and could be safely administered under medical supervision, the opinion was struck down by the DEA's director. The drug became illegal, and the black market boomed. Next came Ecstasy of questionable quality and potency. DanceSafe, a nonprofit that tests the purity of pills at raves, reports that dangerous adulterants like the cough suppressant DXM and the hallucinogen PMA are on the increase, and says these compounds are the prime culprits for Ecstasy-related visits to emergency rooms.