Monkey gone to heaven

In Part 2 of Salon's series on Ecstasy, a controversial study on E's effects on the brain creates fear; a breakthrough moment in MDMA's therapeutic use sparks hope; and Generation X ponders its drug days ahead.

Published July 31, 2003 7:54PM (EDT)

Was the X getting worse? Alexander Shulgin, one of the drug's pioneers, says the question is "clouded by the fact that over 50 percent of stuff called Ecstasy is not MDMA." What else could it be? Caffeine, amphetamines, ephedrine, PMA (an Ecstasy-like drug that's particularly dangerous) or other foreign agents that have masqueraded as the real thing for decades.

MDMA itself has been on a wild ride, as illustrated by a timeline that details milestones in MDMA research. (It appears in the appendix of Dr. Julie Holland's "Ecstasy: A Complete Guide.") In 1953, for example, the U.S. Army Chemical Center gave MDMA to lab animals at the University of Michigan (an idea soon abandoned). Then there's Sept. 8, 1976, the day Shulgin took MDMA for the first time (16 milligrams, with no effect). There's MDMA's Schedule 1 status in 1985, and the government's $54 million effort in 1999 to educate the public about "club drugs." But since Holland's book was published, there have been two MDMA tipping points that aren't included in that timeline. They're huge.

The first was on Nov. 2, 2001. What Holland calls the "biggest moment" in terms of MDMA research had the misfortune to be announced two months after 9/11. But it was on that day that the FDA approved the first psychotherapeutic study of MDMA on humans, to be sponsored by the Multidisciplinary Association for Psychedelic Studies, (MAPS), a nonprofit organization that aims to develop MDMA into an FDA-approved prescription medicine. MAPS will study the use of MDMA and psychotherapy for the treatment of patients with post-traumatic stress disorder (PTSD).

Subjects in a Charleston, S.C., clinic will undergo two therapy sessions, three to five weeks apart, at which they will take a capsule of 125 milligrams of MDMA. Between the two capsules, patients will have three non-drug-assisted therapy sessions (pre- and post-administration of the MDMA). "What we're saying is that MDMA is not the therapy by itself, nor is psychotherapy the treatment by itself, but MDMA-assisted psychotherapy is the course of treatment," says Rick Doblin, who founded MAPS in 1986 and has a Ph.D. in the regulation of drugs from Harvard's Kennedy School of Government. "It's not 'Take the pill and then you're happy like a rave'; it's 'Take the pill and then go deeper into the pain,' which facilitates a cathartic process. In that sense what we are doing is the opposite of the way many people use the drug. One of the advantages of MDMA, why people really like it, is that it focuses on the moment. The idea is to work with post-traumatic stress disorder patients so that after the catharsis they can distinguish that the moment they are in is different from the moment they were traumatized -- that every corner they turn is not likely to hold the rapist or assailant."

After a number of delays, and some "stonewalling" by the DEA, Doblin says MAPS is optimistic that the clinical study will start this September.

The other major news in MDMA research was released last fall, blanketed the media, and scared a lot of people, including many of my friends. In the Sept. 27, 2002, issue of Science magazine, Dr. George Ricaurte, a neurologist at Johns Hopkins, published the results of a study called "Severe Dopaminergic Neurotoxicity in Primates After a Common Recreational Dose Regimen of MDMA ('Ecstasy')," aka the Monkey Study. Ricaurte, aiming to mimic human Ecstasy habits, gave five monkeys high doses of MDMA every three hours. He couldn't actually give all the monkeys three hits of E, because one monkey died, and another didn't look so good after his second hit, so they stopped giving the poor ape the drug. The drug damaged tiny branching fibers that allow the dopamine-secreting neurons to do their job. In other words, the monkeys lost dopamine cells, which affect thinking and movement. When you lose too many of these brain cells (a lot, like 80 percent), you may experience symptoms of Parkinson's disease (tremors and other body imbalances). "We know that it happens in monkeys and baboons," writes Ricaurte. "We don't know if it happens in human beings as yet."

"This is the first time anyone's shown dopamine reductions in primates, so everyone got really freaked out," says Holland. "What has never been proven is that there is any damage to the dopamine system in human MDMA users, even heavy users." What's more, Holland and many others argue, the doses used by Ricaurte were much higher than what people typically use.

What's clear is that no one -- not Holland, not Shulgin, nor any MDMA expert I talked to who feels the war on E is misguided -- thinks popping too many pills in one evening is a great idea. "Any drug has a recommended dosage," Holland says. "The reality is, the more E you take, the more you put your brain at risk."

"Nobody knows for sure if your brain would go to completely normal if you stopped taking Ecstasy after you'd been taking it for a long time," says Dr. Jean Lud Cadet, chief of the molecular neuropsychiatry branch of the National Institute on Drug Abuse (NIDA). "There are now a lot of papers showing that people who have taken Ecstasy for an extended period of time can have sleeping problems, be depressed, and have memory problems. But we need to do more studies to study people who have stopped taking the drug for a long time to see if these symptoms go away completely."

Cadet, one of the country's leading researchers on the clinical effects of drugs on the brain, has a tasteful office at a branch of the NIDA on the Johns Hopkins campus in Baltimore. A photo of his handsome, dreadlocked 15-year-old son sits on his desk.

"What do you tell your son about Ecstasy?" I ask him. He proudly explains that he shares his research with his son, who in turn gives talks on the effects of E at his high school.

Right now, Cadet is studying the effects of MDMA exposure on prenatal rats, an area that is no doubt of interest to my ever-growing group of pregnant friends. Cadet found that the babies of pregnant rats who were given MDMA showed changes in some genes in their brains when compared to the genes of babies from pregnant rats that were not given MDMA. While it's still too early to know if the behavior of the baby rats who were exposed to MDMA will be affected, the brains of the little rat pups definitely look different.

I like Dr. Jean Lud Cadet. He's an inviting man. Wearing a hipster short-sleeved button-down, he's comfortable explaining his complicated research in layman's terms. I like that he says, "These drugs are not going to fry your brain like an egg, but research shows that they are toxic." I like that when I ask him if despite the toxicity, many people feel that the upsides of the psychological breakthroughs, the empathy and the intimacy, are worth the potential downsides, he thinks about that for a few seconds and says, "Well, that's a decision someone should make personally, but you can't ask the FDA to approve it." I like that he's working on building better models about how MDMA affects the central nervous system, so if the worst fears about what MDMA does to your brain are true, through his and other research we'll come up with restorative treatments.

The trouble with relatively new drugs is that the real trials take place outside of the lab -- in the love puddles, at the raves, in the desert.

"We test medicine for many years -- but with drugs, people often test themselves," says Mark Gold, chief of the division of addiction medicine at the University of Florida McKnight Brain Institute. He keeps a huge poster detailing Ecstasy use, abuse, emergency room visits and deaths on the wall of his office. "The research is really, 'How many people have become addicted or ended up in emergency room?' It's all done on the fly."

We do know that according to the U.S. Substance Abuse and Mental Health Administration (SAMHSA) in 2001, the number of Ecstasy-related emergency room visits rose to 5,542, up from 4,511 in 2000 and 2,850 in 1999. To put that number in perspective, that's about 3,000 more E.R. visits related to Ecstasy than for LSD, and 88,000 less than for heroin. (There were 61,000 antidepressant-related trips to the E.R. in 2001, in case you were wondering.)

When I was in high school, I had heard of E, but certainly didn't know anyone who had taken it. That was the early '80s. Cut to 2002, when Monitoring the Future (MTF), an organization that tracks trends in teen drug use, found that the increase among 12th graders using Ecstasy was the largest jump of any drug in its 26-year history of tracking teen drug use (11.7 percent have tried E), though in the past year teen use has dropped a bit, to below 11 percent. SAMHSA reported 63 Ecstasy-specific fatalities in the year 2000, most due to heatstroke, and occasionally due to hyponatremia, which is death by drinking too much water. Overdosing on E, in the sense that we think of someone OD'ing on Oxycontin, coke or heroin, is extremely rare.

Victor, for one, has never ended up in the E.R., but he does think all this E has been bad on the brain. "I've suffered some permanent memory loss -- both long- and short-term. Yes, it has something to do with the fact that I am older. And yes, there's the fact that I have been doing recreational drugs for 17 years. But I feel like after I take E, my mind is worse."

"I think I was one of the few voices in the group in the early days who was suggesting that we exercise some moderation," says Sarah (not her real name), a 32-year-old who works in the natural foods business in Northern California. "I knew many people who complained of mild depression the week following a particularly indulgent weekend, and one person who went into it hardcore and basically battled depression on a big scale. Eventually, he wound up going on multiple and varied hardcore antidepressants, with very little success. I think the initial reaction of the group when I brought this stuff up was that I was harshing their mellow."

That attitude has changed. Now we're very curious: Does Ecstasy cause irrevocable brain damage? Will we get Parkinson's? Will we become depressed? Will our kids be fucked up? Empirically, there is an answer. We just don't know what it is yet.

In the short term, the $20 question is whether it's addictive. Here, the experts disagree. "The answer to this is a definite yes," says Dr. Cadet. "Ecstasy can influence the same feel-good systems that drugs like cocaine and speed stimulate."

Dr. Holland disagrees. "I don't believe a physiological addiction has been demonstrated," she says. "I work in the psych E.R. where I routinely treat people addicted to alcohol, cocaine or heroin -- and I have never seen a case of Ecstasy addiction. But I will say that people can become psychologically addicted to any activity, from surfing the Internet, to compulsively having sex, to using Ecstasy."

Experts always disagree; that's why they're experts. In the end all you can do is hear them out, add in your own experiences and those of people you know and make your best guess. Talk to anyone who does the drug regularly and there's a good bet you'll hear something like this: When I'm on it, I really want to stay on it. This can lead to compulsive -- and chemically pointless -- pill popping in order to stay high. Bottom line: It may or may not fall under what is considered a physical addiction, but many people still have a psychological jones for it. In the many conversations I had with my friends about Ecstasy for this story, I could almost feel their heart rates increase when recounting the great early E experiences. E remains exciting stuff -- even when it worries us.

Checking back with the four monkeys who survived Ricaurte's über-doses is one way to find out E's long-term downsides, if any. Of course, the doctor's subjects will still be overdosed monkeys, not humans. Checking back with my friends in another 15 years -- when many of us will be celebrating our 50th year on earth -- might be a more natural laboratory in which to observe the drug's long-term effects.

- - - - - - - - - - - -

Hawkeye from "M*A*S*H" liked to say: Nothing exceeds like excess.

The Buddhist philosopher Alan Watts famously wrote: When you get the message, hang up the phone.

For the past few years, my Ecstasy club has been teetering in between these two notions. We're beginning to realize that drugs are many things, but in the end they are just that: drugs.

What, after all these years, are we trying to cure? And how will we continue to do the work of self-medication as the E wears off, whether through total abandonment of the drug or tapering?

Ecstasy showed up at a time in our lives when our need for intimate human connections was bigger than our desire to be independent -- Rushkoff's post-caveman clan theory. Now, with most of us over 30, many closer to 40, we've got real jobs at real companies, and are in committed relationships with partners with whom we share real mortgages and may even raise real families. "When the order of business is no longer how to lose the self," says Rushkoff, "that's not the moment you take E."

For my friends who, I believe, represent a cross section of the adult recreational E user, there's something of a split. Some are going to slip further into the self, retreating into one version or another of a happy domesticity, full of fond memories of their roaring 20s and 30s. Whether their minds have learned all they can from MDMA, or their bodies have simply had enough, they've gotten the message: Recreational drugs are best left to the young.

"It seems so stupid to me now, to keep trying to get what she's having or what they're having or what I remember having, only to be reminded an hour into a session of chain-smoking and teeth-grinding that X just doesn't cut it for me," says Robert, the carpenter, who now lives in Sweden. "I'm not saying that I have not had good times on the shit. But on the whole, I have trouble rationalizing its use based on a few isolated incidents of pure wonder."

Others will keep moving down the buffet line. "I find myself drifting to pharmaceuticals," says Victor. "You can trust the quality, you can trust the effects, and you don't feel that bad afterwards. It feels like a more sustainable activity."

Probably so. What worries me is not the weekend Vicodin warriors, but my friends who might go deeper and deeper into harder drugs -- speed, coke, ketamine and worse -- drugs that have the ability to mess up their lives in a way that E never did. I fortunately don't know too many people going down those roads. And the government's much-repeated "gateway" effect -- each drug leads to a harder drug -- was recently discredited by the RAND Drug Policy Research Center.

Still, Dr. Holland reports that for the first time at the Bellevue Psychiatric emergency room, she's seeing people who are on crack, heroin and PCP, who are also using E. "The fact that Ecstasy is now another drug of abuse to the Bellevue crowd is a major change from the last two years," she says. "When people start smoking it or shooting it up is when you really run into trouble." No, those people aren't representative of the vast majority of recreational E users, but when a drug has gone from the dance club to the crack house in just a few short years, there's cause for concern.

Most of my friends think they will continue to use Ecstasy in moderation. "There's been a learning curve in a certain milieu of people who were taking E all the time," says Pippi, now pregnant. "The two-pill nights are way behind me -- with a child it has to be. The occasions in the future will be very, very special." Before we get off the phone, she mentions that she can't wait to stop nursing because she has two hits of really good stuff that she's preserving for a special weekend with her husband.

"I don't do it much now, but I still love X," says Vicki, 34, recently married and living in Los Angeles where she works as a copywriter and volunteers at a suicide hotline. "Even being currently pregnant and drug-free hasn't stopped me from advising every adult who mentions it to try E, just once, to see for one night what it's really like to open your heart to the people around you -- or to your desk and doorknobs, if you stay home -- and feel truly blessed."

"I may be one mischievous middle-aged babe who sneaks in the occasional candy-flip [Ecstasy and LSD together] just to keep me spry," says the still 20-something Suzanne. "I think people will grow nostalgic for their E days, especially the group dynamic. I can see it as a reunion thing."

While Dr. Cadet doesn't waver from his opinion that MDMA is a deadly drug for monkeys, rats, humans, and other creatures, he's optimistic. "What's going on with Ecstasy may be similar to what's happening with HIV. A lot of older gay men saw their friends dying and changed their behaviors regarding sex. As people get older and more papers come out about the clinical effects of drugs like MDMA -- memory loss, serotonin depletion -- the hope is that some of the people who have been using the drug will say, 'I don't want these things to happen to my brain.'"

Organizations like DanceSafe are a good sign that the next generation of Ecstasy users want to keep their brains intact. A peer-based nonprofit that runs on volunteers and donations, DanceSafe works to educate the buzzing world about nightclub safety, but in a way that the rave and nightclub community (and others who are young at heart) can relate to, rather than via scare tactics or egg-frying PSAs. For the past four years, its volunteers have set up tables at clubs where they test pills (so E users know if what they are about to swallow is actually MDMA), handed out ear plugs, pointed out fire exits, and generally worked to decrease the number of E.R. visits among young people. The organization's excellent online slide show, "This is Your Brain On Ecstasy," details exactly how the drug works.

Time will ultimately tell my friends and me how our brains did on E. MDMA pioneer Shulgin concedes that "there may indeed be some changes in the brain that are slow to recover," while at the same time he regrets he hadn't encouraged more MDMA-using therapists to publish their findings. With the MAPS study on the drug's psychotherapeutic properties moving forward, the history of MDMA, interestingly enough, loops back on its beginnings. Shulgin himself is working on discovering another, perhaps less controversial potion with similar upsides. For now, he hasn't had much luck. "There are many compounds with fascinating psychedelic properties," explains a man who has discovered or rediscovered more than 200 mind-altering chemicals in the past 40 years, "but none with the unique magic of MDMA."

MDMA and I have ridden the bell curve: Curiosity led to a little experimentation, then lots of use, some great times, and then too much teeth-grinding. Now, my best guess is that I'll continue to use it with extreme discretion; I'm probably closer to my last pill than my first. My adventures in MDMA have taught me a few things about myself. Although I am someone who for years found nothing more tedious than talk therapy, the lengthy conversations and connections I've had with intimates old and new have been life affirming and important. I tend to stay guarded, yet there's an expansive and emotional person who springs out like a jack-in-the-box after popping a pill. Fortunately, I'm beginning to understand that if you can't incorporate what you learn from a positive drug experience into the waking life, but rather need to endlessly repeat it searching for that same high, it's a useless experience. There's that and the fact that (to paraphrase Clements' "Dog"), despite all this talk about consciousness-raising, much of our time was spent simply lolling about in a love puddle. One can only loll so long.

The woman I first took E with 15 years ago remains a close friend. After a couple of margaritas, we've been known to get a little nostalgic for that first perfect night, with that first perfect hit. Although I no longer pine for it, or her, when I look into her eyes, I can still see traces of that unique magic. I suspect I always will.

By Larry Smith

Larry Smith has written about his and other people's lives for ESPN magazine, the New York Times, Teen People, and other publications.

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