Post article on Ecstasy studies

[crank47]

http://www.washingtonpost.com/wp-dyn/articles/A14627-2002Sep28.html

On Ecstasy, Consensus Is Elusive

Study Suggesting Risk of Brain Damage Questioned by Critics of Methodology

By Rick Weiss

Washington Post Staff Writer

Monday, September 30, 2002; Page A07

New research has escalated a decades-old scientific and political battle over the risks inherent in the popular street drug known as Ecstasy.

A synthetic chemical cousin of "speed," Ecstasy already had a rap sheet as long as its chemical name: 3,4-methylenedioxymethamphetamine, or MDMA. Studies in animals have suggested it may be toxic to brain cells that help regulate mood. It's been linked to memory impairment in some users. And rarely the drug triggers a mysterious reaction in which the body becomes radically overheated, causing sudden death.

If that weren't enough to make potential users think twice, Ecstasy is highly illegal. The Drug Enforcement Administration (DEA) has placed it in its most restrictive "schedule 1" category, meaning it has no medical value and carries serious risks.

Last week, researchers added to the agony of Ecstasy by reporting in the Sept. 27 issue of Science that, in monkeys, at least, even one night's indulgence in the drug may increase the odds of getting Parkinson's disease. Yet despite all the evidence against it, Ecstasy's popularity has only grown in recent years, with about 10 percent of U.S. high school students saying they've tried it in the past 12 months. That pattern is testimony to the profound sense of peace and open-heartedness that Ecstasy users say the drug delivers. But it is also the result of a deep distrust of the evidence of Ecstasy's harm -- not only by youthful partygoers but also by a cadre of scientists and others who have been arguing with increasing fervor that much of the work, including the latest study, is flawed.

A close look at the evidence presented by both sides shows how difficult it can be to judge the long-term significance of drug-induced changes in the brain.

Ecstasy produces its pleasurable effects largely by making neurons secrete massive amounts of serotonin, the same chemical that is the target of some antidepressants. Studies in monkeys -- and less definitive studies in people -- have suggested that Ecstasy can damage the tiny branching fibers that allow those neurons to communicate with nearby cells, perhaps permanently.

George Ricaurte, a Johns Hopkins University neurologist who has led many Ecstasy studies, said the evidence is overwhelming that the drug is dangerous. "My belief and the belief of the vast majority of others is that the [serotonin-producing] nerve endings are destroyed by the drug. It is a pruning, if you will."

Others, however, strongly disagree. They say results in animals have varied so much from species to species -- and the doses given the animals have been so high -- that extrapolation to humans is unreliable. Moreover, they say, human studies have rarely controlled for concomitant use of other drugs (some scientists think the small memory decline seen in some Ecstasy studies is actually due to participants' use of marijuana). And the few human brain scan studies that have been published used old and untrustworthy imaging technology.

"In my opinion . . . these studies are so flawed in terms of the technology used that one cannot derive any conclusion from them at all," said Stephen Kish, another leading Ecstasy researcher and chief of the human neurochemical pathology laboratory at the Center for Addiction and Mental Health in Toronto.

The newest study, led by Ricaurte and involving monkeys and baboons, sought to more closely mimic human Ecstasy use by giving three consecutive doses of the drug at three-hour intervals -- as if the animals were at an all-night "rave." In contrast to previous human studies, brain scans found evidence of damage not only to serotonin neurons but also to neurons that produce dopamine.

Dopamine levels were down about 65 percent six weeks after the test. If those reductions are permanent, Ricaurte said, users may be vulnerable to early-onset Parkinson's (which is caused by reductions of about 90 percent) when levels drop further as a natural result of aging. "The margin of safety for MDMA appears to be extremely small, if present at all," he said.

Alan Leshner, former director of the National Institute on Drug Abuse (NIDA) and chief executive of the American Association for the Advancement of Science, which publishes Science, agreed. "This says even a single evening's use is playing Russian roulette with your own brain," he said.

Critics, however, noted that the drug was given in human-equivalent doses but was injected into the animals, a route that Ricaurte himself has shown to be twice as potent as taking the drug orally. Adding to evidence that the test involved overdoses, two of the 10 animals in the experiment died quickly after their second or third dose and two others became so sick they could not take the third dose.

"How come 40 percent of people who are doing this drug are not dying or almost dying?" asked Rick Doblin, president of the Multidisciplinary Association for Psychedelic Studies, a Sarasota-based organization that funds research on therapeutic uses of mind-altering drugs.

Several experts said Parkinson's symptoms have never been associated with Ecstasy users -- even those who have been taking it regularly for years. Some called the new work the latest in a string of biased studies sponsored by the federal government.

Federally funded research on Ecstasy is "an egregious example of the politicization of science," said Charles Grob, a neuropsychiatrist at the University of California at Los Angeles School of Medicine, in testimony last year before the U.S. Sentencing Commission. "Much of the NIDA-promoted research record . . . suffers from serious flaws in methodological design, questionable manipulation of data, and misleading and deceptive reporting in the professional literature and to the media."

Kish of Toronto said the one serious risk clearly linked to Ecstasy is "malignant hyperthermia," an unpredictable onset of high fever and sudden death. He said New York, a city estimated to have thousands of users, experiences about one death a year linked to Ecstasy by itself and about seven a year involving Ecstasy with other drugs. Leshner's Russian roulette analogy only makes sense, he said, if one imagines a gun with one bullet and "thousands and thousands and thousands of chambers."

To be sure, Kish said, that risk is not zero and needs to be taken seriously. And the picture could get worse when definitive human brain imaging studies are completed in the next year or so. New, high-tech equipment being used in those studies should settle the question of neuronal damage.

But if the results amount to something less than an indictment, then scientists will have to consider whether the potential psychological benefits might in some cases be worth the risks. That will require a new batch of studies, looking not for damage but for evidence of healing.

Last fall, the Food and Drug Administration gave the green light to the first such study, which would test Ecstasy's usefulness as an adjunct to therapy for people with post-traumatic stress disorder as a result of sexual or other violent assaults.

That study, sponsored by Doblin's organization and set to take place in Charleston, S.C., is awaiting approval by the DEA.

Marsha Rosenbaum, a director at the New York-based Drug Policy Alliance, warned that anti-drug advocates could harm their own cause by just saying no to the possibility that some illicit drugs might be therapeutic.

"Like everyone, young people stop trusting you when you bend the truth to scare them," Rosenbaum said in a statement. "Good science, not misguided fear, is what helps us talk honestly and effectively with our teenagers about drug use and their safety."

© 2002 The Washington Post Company

[vicman]

reading this reminds me of the studies done on saccharin, when it was discovered that saccharin (sweet & low) caused cancer in lab rats....media made a big deal out of it 'cos every low or non-sugra product had saccharin back in the day...what they had failed to mentioned was that lab rats were being administered an equivalent dose of 10,000 packs of the stuff everyday for 10 years before they developed cancer.

extrapolating that to humans would mean that someone would have to consume about 1,000,000 packs of the stuff everyday for 10 years.

highly unlikely.

which also leads me to thnk, that MDMA has been widely popular in the UK for a very long time so a study population with 10+ years of using the stuff is readily available over there. additionally wht other confounders arealso involved with the minimal studies done w/ humans? have they been using other drugs? medications? etc?

[crank47]

werd vic. The studies (on pretty much anything, not just MDMA)done in the US are incredibly biased depending on who's funding them. I find much of the work done in the UK tends to be much more objective and some of the latest ones on MDMA aren't finding all the damage the US studies claim it causes. I think one I saw over the summer found it to be no worse than Prozac which is friggin prescribed like candy here in the US.

[malanee]

I would also like to see studies comparing the long term effects of ecstacy use with the use of other drugs/alcohol. I read somewhere that the effects may be no more harmful than the effects of anti-depressants.

I fully believe that long term use of ANY drug has an effect on brain chemistry. But I'd like to know the hard facts - not media hype and BS.

Educate and inform - scare tactics never have and never will work with the younger generation.

~Malanee

[cookiegirl]

-- good to see some balanced reporting out there. . .

[vicman]

the best source of info would be scientific journals...lots of 'em, to give you a better idea of the facts...media is all hype

[hotcheme]

Originally posted by vicman

additionally wht other confounders arealso involved with the minimal studies done w/ humans? have they been using other drugs? medications? etc?

i don't think a realistic study could be conducted in comparison with the e used in clubs because there is no way to study the effects of ecstasy combined with all the other substances used to fill those pills.

regardless i don't think i would ever beleive a study that said e has a minimal risk based on my own experience with the drug.

[vicman]

well a study on w/ human subjects would be virtually impossible. ethically it would not fly, would never get clearance. giving people something that can be harmful to them..although tuskegee would suggest otherwise, but anyway, lots of people have allergic reactions to lots of comon medications out there that one can get over the counter. some people are allergic to penicillin, asprin, etc.

i recall a few years ago the whole thing going on with ephedrine. diffeerent individuals have different reaction to different drugs (thats why anesthesiologists get paid top $$$). personally, i've never had a horrible experience while rolling, but thats just me.

[malanee]

Hey Vic - they can't give people ecstacy and study them. But they CAN study current ecstacy users. They actually do that a lot with cocaine and heroine users.

[merkie]

I agree. I have never heard/seen a conclusive study that shows the ill effects. Obviously it can not be good for your brain, but I am tired of hearing about it creating "holes in your brain" (thanks to Opra for boradcasting that genius theory) and causing Parkinson's disease. No study has been true-to-life. They were injecting the MDMA directly into the monkeys' arms. (no human injects it; at least not that I know of). Also, Liz said that she read that they were injecting them with extremely high doses (I think she said equivalent to 10 pills because they said that that was one night of partying for the avg. partygoer). I know some people take that many, but not the avg person. Of course it is going to have ill effects on them.

I want "real" proof. I see validity behind e causing mood changes, but not the other things it is being charged with.

[crank47]

Originally posted by vicman

well a study on w/ human subjects would be virtually impossible. ethically it would not fly, would never get clearance. giving people something that can be harmful to them..although tuskegee would suggest otherwise, but anyway, lots of people have allergic reactions to lots of comon medications out there that one can get over the counter. some people are allergic to penicillin, asprin, etc.

Tell that to JHU!

Actually, a good friend of mine did a study last year with JHU. She was paid to participate and she was reimbursed for her costs in getting what was needed, since they couldn't legally supply her with the drugs. Basically she had to talk to Larry all day for a month and went in 3 times a week to have a bunch of tests done (including brain scans). She was a bit of mess at the end of it and took a well needed rest (she has also never spoken with Larry again). BTW, she found about it from one of her friends that did a previous and similar study there, but had to talk to Mary Jane instead.

[vicman]

Originally posted by malanee

Hey Vic - they can't give people ecstacy and study them. But they CAN study current ecstacy users. They actually do that a lot with cocaine and heroine users.

would they give people free pills? i mean, then whats in it fer me, you know?

yup, ur right...they do it with cocaine users.

[crank47]

Originally posted by vicman

would they give people free pills? i mean, then whats in it fer me, you know?

yup, ur right...they do it with cocaine users.

They can't give illegal drugs, but they reimbursed for costs the participant incurred during and for the study.

[hotcheme]

but even if they are doing an observational study of ppl who are already using e, how can they be sure it is e? i mean, very few pills now are pure MDMA so any tests may be showing the effects of whatever filler is in the drugs.

and if you are respsonible to go get your own pills for the study, do they test the pills first to know what they are observing?

[crank47]

I haven't heard of any studies like this on MDMA. Larry and pills are two very different beasts. I don't think you could be on MDMA during all your waking hours, while it is possible with Larry, and pills and Larry are cut with very different substances. I'm sure if a researcher was serious about it, they could figure out a way to do it though.