The big E

Doctors, law enforcement and ravers are scrutinizing ecstasy's possible long-term effects as the drug pours into the U.S. in record numbers.

Topics: Drugs,

It’s been less than an hour, and you can already feel it. The corners of your mouth are starting to lift up, creating a big semicircle, a Cheshire grin. The pit of your stomach, normally so weighed down with stress, is lightening. You’re giddy, like the first time you fell for someone. The pupils of your eyes are dilating, growing with excitement. You look around and announce to the world that you’re in love — with everyone and everything. Suddenly a new feeling hits; you realize it’s all been foreplay until this instant, a slow buildup of excitement that you couldn’t stop. But now, before you realize it, before you can control it, it’s here. You want to let out a scream; you are so fucking happy. It’s like the best moment in your life.

And all it took was just one pill, one gulp of water and $20.

There’s a reason why this dose of happiness — methylenedioxymethamphetamine (MDMA) — is called “ecstasy.” It’s a swallow of pure bliss — triangular, circular and diamond-shaped bliss.

Sam, a 29-year-old writer, has become completely smitten with E (also called the “love drug,” “XTC” and just plain “X”) since he made its acquaintance about a year ago. “It’s the most amazing feeling in the world,” he says. “It just makes you want to touch everybody and be touched by everybody. When you’re in a club and they’re playing good music, it becomes the best music you’ve heard in your life.”

Why not transform any old techno beat into the best mix you’ve ever heard? A simple hug into a sensual tactile experience? Taking E is like trading up for one night to first class, where everything seems a hundred times better.

But for every chemically induced pleasure, it seems, there’s a price. Excessive use of ecstasy has long been suspected to cause neurotoxic effects — i.e., brain damage. But a new study raises the stakes; it posits that only a few uses of the drug can cause permanent impairment. And some researchers see other long-term problems as well — including, ironically enough, depression.

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MDMA isn’t a new drug — it was patented before World War I by the Merck drug company, and rediscovered once before, in the ’60s. Ecstasy has been illegal in the United States since 1985, when it was put into “Schedule 1,” the most dangerous drug class, which means it is considered to have no medical value. (Even cocaine doesn’t fall into this category, because of its use in anesthesia.) But ecstasy is now moving its way up America’s drug-popularity ladder and being closely watched as a consequence. U.S. Customs has seen a surge in the amount of ecstasy being smuggled into this country, and has confiscated more than 1 million doses in just the first eight months of this fiscal year. (In comparison, only 375,000 tablets were seized in the previous year.)

“This has mainly been used by middle-class college students, but the fact that this is pouring in here now, primarily from Western Europe and the Netherlands [creates] a real worry that we could see street dealing of this stuff,” says Dean Boyd, a spokesman for U.S. Customs. “What Colombia is for cocaine, the Netherlands is for ecstasy.”

The drug isn’t produced in the United States in any sizable amount; as a consequence, suppliers in Europe are capitalizing on increasing demand here. Boyd says that as the market grows, its distributors are changing as well, from the dorm dealer to the drug world’s more traditional retailers. “Once you get organized crime involved, that’s where it gets transformed from the drug that college friends might have to one with a real potential for violence,” Boyd says.

You’ve probably seen the eggs-in-a-frying-pan commercial describing the harmful effects of taking drugs. To paint a picture of what your brain looks like on ecstasy requires a walk through cranial byways of the brain, and through doctors’ vastly different interpretations of what happens when you take it. Is E, which is not physically addictive, the harmless “soft drug” users think it is? Or is it just sneakier than other drugs, inflicting injury without the telltale signs caused by other drugs?

Its partisans love it. “I think my life is pretty good and I wouldn’t want to do anything to wreck it: I would never do cocaine or speed because I don’t like that loss of control, and I would never do anything addictive,” says John, a San Francisco dental student. “Ecstasy is a safer escapism, and you still have your wits about you.” John says the first time he took ecstasy, he felt like he could sit down and do calculus — because, unlike alcohol, it didn’t affect his ability to concentrate.

But researchers are increasingly contending that the attitude of users like John is naive. Contrary to widespread rumors, doctors say ecstasy does not drain your spinal fluid; but it does have negative effects. “There’s no such thing as recreational ecstasy use; this is not like playing ping-pong or tennis,” says Dr. Alan Leshner, director of the National Institute on Drug Abuse. “We are very concerned because of its rise in popularity and how people claim that it doesn’t have a big effect … Whether or not it produces physical dependence is not relevant. Methamphetamine and crack cocaine don’t cause physical dependence according to physical medical criteria, but they are among the most addicting substances ever known to mankind.”

New research on primates funded by the National Institute on Drug Abuse and reported in the June 15 issue of the Journal of Neuroscience concludes that the use of ecstasy just a few times can lead to long-term brain damage in squirrel monkeys. The report is a scary development for those who have just flirted — and are not in full-blown relationships — with ecstasy. “Most people who use MDMA don’t die or have psychiatric problems right afterward,” says Dr. Una McCann, associate professor at the Department of Psychiatrics at Johns Hopkins University and one of the authors of the study. “This makes people think it’s safe. I think the danger is people are slowly damaging their brains and are totally unaware of it. I think the older they get, the [users] will be much more vulnerable to a variety of problems such as depression, memory disturbances, anxiety disorders and sleep difficulties.”

MDMA works by increasing the levels of certain of the brain’s neurotransmitters: dopamine, norepinephrine and, particularly, serotonin. The last of these is important in many things — in the body’s regulation of mood and its sense of well-being, as well as in regulating anxiety, sleep, appetite and body temperature — and E users end up with a massive amount of it in their brains. The problem, doctors say, is that MDMA functions almost like a laser-guided weapon that destroys what it hits: the nerve terminals, which are the parts of brain cells that release serotonin.

“Clearly, the amount of MDMA is important, but it’s also important to recognize that even a single dose of MDMA may be enough to produce neuro injury,” says Dr. George Ricaurte of Johns Hopkins University, lead author of the recent study. Besides the recent primate study, Ricaurte has done myriad other tests on human ecstasy users. “By contrast, if you consider the case of alcohol, it’s only in long-term alcoholics where one senses changes in brain structure.”

Ricaurte concedes that since his study was done not on E-using ravers but on primates, there is room for uncertainty about its effects on humans. He says the amount of the drug the researchers gave the monkeys was high. The point of the study was to find out whether the monkeys’ bodies could repair E-induced brain damage once it was incurred. Twice a day for four days, Ricaurte and his researchers gave squirrel monkeys either ecstasy or salt water. Two weeks later, they killed part of the test sample and looked at their brains. McCann explains that for E to qualify as neurotoxic in their study, there had to be damage remaining after two weeks. There was.

Six or seven years later, the researchers killed the remaining monkeys and found that, although the serotonin neurons recovered in certain parts of the brain, there was still damage remaining elsewhere. The areas particularly affected were the neocortex, which is important for conscious thought, and the hippocampus, which is critical for long-term memory.

“Ecstasy is a great drug,” says Dr. Bill Wilson. “It’s just too bad it’s so damn neurotoxic.” Wilson is a professor of pharmacology at Duke University Medical Center and co-author of the 1998 book “Buzzed: The Straight Facts About the Most Used and Abused Drugs From Alcohol to Ecstasy.” “Ecstasy falls into the category of ‘extremely dangerous’ because you can use other drugs like alcohol or cocaine 50 or 100 times and still recover from it with drug treatment,” Wilson says. “But you can’t recover that lost serotonin function in your brain — there’s nothing to do to recover that. It’s gone forever.”

Other scientists disagree. They dispute that MDMA is neurotoxic, and find flaws in both the test methods in animal tests and the studies that have involved humans. For the tests on humans, critics say there’s no way to tell for sure that the subjects had been using pure MDMA. Ecstasy is often cut with other drugs, so it would be difficult to tell whether it was the actual X doing the damage or the other drugs in the mix.

“From a scientific standpoint, there is no evidence that it causes brain damage in humans,” contends Dr. James P. O’Callaghan, head of the molecular neurotoxicology lab at the Centers for Disease Control and Prevention, who has studied MDMA’s effects on the nervous system. “Because these drugs act by releasing serotonin, you have to have terminals there for the drug to act on. By definition, you can’t be destroying the machinery if the drugs continue to work.”

Dr. Charles S. Grob, professor of psychiatry at UCLA School of Medicine, also doubts claims of MDMA’s neurotoxicity. He was one of the few doctors to get FDA approval to study MDMA in humans. After looking at its psychological and physical effects in 18 volunteers, he found no changes in their memory, and only a few complications with the blood pressure of some of the users, particularly those on other medications.

Grob wants to continue studying the therapeutic effects of MDMA on humans, but hasn’t received FDA approval to do so. Because it’s such an emotionally intense drug, he says he believes MDMA can be very effective in treating post-traumatic stress disorder and obsessive-compulsive disorder, and can serve as an emotional and psychological aid to patients with terminal illnesses.

However, even proponents of therapeutic MDMA use say that recreational use can be dangerous. For example, Grob’s study was done in a clinical environment, where it was cool and doctors were monitoring the subjects, who were lying in bed. The setting was vastly different from raves or clubs, where users are more likely to overheat and not replace their fluids — leading to risk of lethal hyperthermia, which has been responsible for some of the MDMA-related deaths.

“MDMA might have great potential to have a great value, but because you have a user culture which has been using it excessively and in dangerous ways, it has proved impossible to research,” Grob says.

Because it has been impossible to research this different side of MDMA, the effects of it in psychotherapy are mostly anecdotal. But at least one woman can testify to its benefits.

Rafaela is the therapeutic face of E. She credits the drug — literally — with her survival. For the first 17 years of her life, she lived a nightmare filled with sexual abuse; when she ran away from home to find solace, she wound up being held captive for a year, during which she was raped repeatedly and told that if she tried to leave, she would be killed. When she fled her native country in South America for the United States, she tried to put it all behind her. But none of the therapies she tried were successful.

A friend, seeing Rafaela’s desperation (she had already made one attempt to end her life), told her about some psychotherapists who were administering MDMA to see its possible therapeutic effects. After using it with a psychotherapist alongside her, Rafaela says, she worked through years of trauma. She is not the typical user — she’s 40 years old, and has never done any other drugs. Ecstasy was still legal when she took it back in 1983.

“Before, therapists would always be trying to make me be angry; they said I wouldn’t be healed unless I felt this anger that I couldn’t feel,” she says. “When I took MDMA with therapists guiding me, the only way I can describe it is that, before, I always arrived at a point where there was a wall, where I knew that it happened and that I would back off. Under the right setting and with people that I felt safe [with], I was able to go past that wall, and understand that my anger wasn’t the anger they were making me feel. I wasn’t a person who screamed and stomped, which I thought I was supposed to do. It allowed me to accept it as much as I could and realize that it didn’t have to control my life.” For Rafaela, taking MDMA was worth the risk — what’s the potential loss of some neuro terminals compared to the loss of her life?

But whatever the merits of the arguments over MDMA’s dangers, all involved say one of the most perilous aspects of ecstasy is that other drugs are too often sold under its name. This makes it risky for the user, who might be getting just speed, a mixture of MDMA and ketamine (Special K), PCP or, as was amusingly shown in the recent film “Go,” something harmless, like aspirin.

“Everywhere you turn, someone is trying to sell you E,” says Anne, a raver and user. She is a 20-year-old college student who has used E more than 100 times since she was 14. “But half the time it’s baby aspirin. In L.A., a friend of mine told me they’re selling vitamins as E. The scene has changed; there are people trying to make money now, people who don’t understand the rave culture.” Anne has escaped any bad experiences with E thus far — except once, when it made her vomit.

While there is no way to make ecstasy “safer,” there is a way to at least make sure you’re getting MDMA and not some compound that may have a more adverse affect. Bill Hayley, a 28-year-old in Vancouver, British Columbia, sells a kit called “E-Z Test” that can tell a potential user whether what they’ve bought is MDMA. He says it’s really easy: All you have to do is take a piece of a pill and drop some liquid on it. If the piece changes to a dark purple, you know you’re getting MDMA. (The test comes with a color chart to help interpret the results.)

Hayley is also is part of a harm reduction program that sets up booths at raves, stocked with bottles of water so people don’t get dehydrated, and instructions on how to take drugs responsibly (even if you believe that’s an oxymoron). “You’re never going to stop drug use; no matter what tests come out, people are still going to make their choice,” Hayley says. “Harm reduction is basically a philosophy or policy that’s dedicated to inform and encourage users to make better decisions so they can reduce the risk of harm while they are doing drugs.” Since last December, when he started selling the kit, he has sold 500, a number he believes will increase as more people find out about the “safer” way to do drugs.

While doctors might cringe at Hayley’s approach, it may be the best way to reach the community of recreational users who dismiss each negative study as just another example of doctors saying something’s bad for you.

“I have spent the last 11 years of my life going to live music in clubs, but there’s no way for me to know whether the amount of loud music will have an adverse affect on my hearing 20 years from now,” says Sam. “I don’t know the price I pay for taking E, but I haven’t been able to set that bar in my mind yet when it’s too much.”

At 20, Anne says she’s still young and if there’s ever a time to take risks, it’s now. She also has a ready plan for what to do if she does end up experiencing the unthinkable: “I don’t buy into it — that we’re the next generation of brain-damaged adults. If I get to be that way, I’ll just take some Prozac. This day and age is insane, there are so many drugs you can take for almost anything. I’m not too concerned.”

Dawn MacKeen covers health for Newsday.

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