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Du henviser til: Toxicodynamics and long-term toxicity of the recreational
drug, 3,4-methylenedioxymethamphetamine (MDMA, ‘Ecstasy’)
G.A. Ricaurte a,*, U.D. McCann b, Z. Szabo c, U. Scheffel c
Science forced to retract article on "ecstasy"
Stephen Pincock
British Medical Journal (BMJ) 327: 579
September 13, 2003
The US journal Science this week published a retraction of a research article that it published last year on the drug 3,4-meth-ylenedioxymethamphetamine (MDMA, or "ecstasy") ( Science 2002 ;297: 2260-3, a move that has prompted questions about the peer review process.
In this week's issue of Science (12 September), researchers from Johns Hopkins University admitted the results of their paper"Severe dopaminergic neurotoxicity in primates after a common recreational dose regimen of MDMA ('ecstasy')" were invalid. Nine of 10 animals in the study had been given the wrong drug -- methamphetamine instead of MDMA -- owing to the incorrect labelling of a bottle, Dr George Ricaurte and colleagues write (
http://www.sciencemag.org) .
In the original paper, the team said doses of MDMA similar to those used recreationally were severely damaging to dopaminergic neurons, something that had not been seen before. In their retraction they note that the combination of dopaminergic and serotonergic neurotoxicity that they found would be quite expected with methamphetamine.
Professor Colin Blakemore, the chief executive designate of the Medical Research Council, told BBC Radio 4's Today programme that the retraction raised concerns about how the paper got into print.
"There is this supposedly rigorous process of peer review. It's very hard to see how that process operated properly in the case of this article," he said.
Professor Blakemore said he had previously queried the journal because 40% of animals in the study either died or were so close to death that they had to be withdrawn.
"Whatever one thinks of the toxicity of ecstasy, 40% of young people using it every weekend are not dying. It's that sort of thing that should not have got past referees."
The journal's view, on the other hand, is that the problem "would have been almost impossible to pick up with peer review," according to a statement from Dr Katrina Kelner, deputy managing editor for life sciences at Science.
She commended the authors for so thoroughly investigating their conflicting data, saying: "For every scientist, one of the main responsibilities is to the accuracy of information in the peer reviewed literature."
"It is the policy of our journal to set the record straight whenever a research article is later found to be flawed," she added.
An article in the New York Times said that unnamed critics have accused Dr Ricaurte of "rushing his results into print" because legislation designed to curb ecstasy use was before the US Congress.
Dr Ricaurte told the newspaper that the accusation was "ludicrous." His laboratory made a "simple human error," he said.
After a series of controversies involving peer review, Britain's Royal Society recently launched an investigation, chaired by Patrick Bateson, professor of ethology at Cambridge.
Professor Bateson said last month that peer review has been criticised for being too secretive, and that some have suggested it provides a way for the establishment to prevent the airing of unorthodox ideas.
"We want to see if any evidence supports such a claim," he said.
COMMENT: The letter from Ricaurte et al. understates by 100% the mortality rate of their primates administered their sequential dosing regimen of MDMA as reported in their paper.
One out of 10 are reported to have died in the letter but 2 out of 10 were reported to have died in the paper. While Ricaurte et al. are among the main proponents of the argument that even one dose of MDMA carries substantial risks and that MDMA use can significantly impair memory, it seems that they are showing symptoms of this deficit in that they seem to have forgotten that just 8 1/2 months ago, they clearly reported in their paper that two animals died. Fortunately, we did not forget.
On June 9, 2003, I brought this to the attention of the letters editor for Science and requested a correction be printed in a subsequent issue. The letters editor said that such a correction did seem required by the obvious difference between the higher mortality rate reported in the paper and the surprisingly lower mortality rate that was reported in the letter.
What I suspect happened is that Ricaurte et al. treated more animals than they reported on in their paper, so that they perhaps did have a group of 10 animals out of which only one died. If that is the case, that still doesn't mean that they can just ignore the other monkey they inadvertently killed prematurely.
Ricaurte et al. stated in the letter that "one of ten monkeys that we treated with our sequential dosing regimen of MDMA that we used died of complications of severe hyperthermia." Yet their paper reports two deaths related to hyperthermia in the ten monkeys treated. They first reported data from five squirrel monkeys, noting "the fifth [squirrel] monkey developed malignant hyperthermia and died within hours of receiving the last dose of MDMA." Later on, they reported data from five baboons, writing "Again, one of five animals [baboon] died, this time shortly after receiving only two doses of MDMA. Malignant hyperthermia (up to 41.6 C) was again an important factor."
This is an important issue since the mortality rate can be used to help evaluate whether the dose Ricaurte et al. administered to their primates actually is a "common" human dose, as they alleged in the title of their paper. Furthermore, the paper reports that another two primates showed symptoms of behavioral toxicity after just two of the three injections and weren't administered the third injection, data not mentioned in the letter. They reported that "One [squirrel] monkey became less mobile and had unstable, tentative gait after the second dose, and therefore was not given the third planned dose." They also reported that "A second baboon appeared unstable after the second dose of MDMA, and therefore received only two of the three planned doses."
MDMA neurotoxicity is a controversial issue. The credibility of Science and of the Ricaurte et al. team is at stake when the number of animals they say died from the doses of MDMA administered declines over time.
False drug information harms kids
By Marsha Rosenbaum
Research Scientist
With little fanfare, highly touted researchers from Johns Hopkins University recently made a stunning announcement. Data from their experiments with the now infamous drug Ecstasy, published a year ago in Science, turned out to be fatally flawed.
It seems the vials had been mislabeled and the drug administered to -- and that killed 20 percent of -- the study's laboratory monkeys and baboons was not Ecstasy but a completely different substance.
As a research scientist, having conducted the first federally funded sociological study of Ecstasy users, I am happy about the recent news that one dose of Ecstasy does not, as the widely publicized Science article had claimed, cause irreversible brain damage leading to Parkinson's disease.
What bothers me is the turn of events that enabled our government to consistently use faulty research to shape bad drug policy.
Ecstasy's story began nearly 30 years ago, when it was first used legally as an adjunct to psychotherapy. Psychiatrists were impressed with its ability to help couples communicate, to enable trauma victims to heal and to soothe chronically ill patients facing death. Ecstasy crossed over into recreational circles in the early '80s and shortly after became illegal. Its use remained relatively quiet until the early-'90s, when it became associated with underground dance parties known as raves.
Ecstasy became popular with growing numbers of young people, and at its peak in 2000, nearly 12 percent of high school seniors admitted to using it at least once. As problems, largely associated with look-a-like pills, overheating and dehydration, were reported, the frenzied print and electronic media ran 1,000 fear-producing stories.
At this point the Johns Hopkins team had released a study showing massive changes in brain chemistry resulting from the use of Ecstasy. Though now considered methodologically flawed and never replicated, the "brain damage" claim resulted in panic.
The federal government couldn't move fast enough, quickly enacting anti-Ecstasy legislation and promoting its $54 million educational campaign to alert young people and their parents to Ecstasy's dangers.
While states enacted laws targeting users, federal legislation was initially stalled but subsequently pushed through as a tag-on to the 2003 Amber Alert bill.
The RAVE (Reducing Americans' Vulnerability to Ecstasy) act held event promoters liable for their patrons' drug use. Since the presence of medical staff and other safety measures at dances or other gatherings constituted awareness that drugs might be used there, sponsors faced an impossible dilemma. They could eliminate "harm reduction" measures such as pill testing and chill-out rooms and risk patrons' health, or maintain them and risk their own arrest and prosecution.
As an educator, the credibility of the Ecstasy educational campaign worried me from its inception.
Drawing from the Johns Hopkins "serotonin" research (now refuted by a recently published, much larger and better controlled study), Web sites and television spots carried frightening "this is your brain" images showing a normal brain alongside an obviously damaged Ecstasy user's brain. Although those images turned out to be phony, the National Institute on Drug Abuse director loudly proclaimed to worried parents and politicians that the government finally had the science to show young people that Ecstasy could have dire consequences.
So much for science, and so much for convincing young people that the government is telling the truth. Indeed, the recent Science retraction is just another nail in the coffin of credibility when it comes to what adults tell young people about drugs. Although those "this is your brain ... " ads (along with the drug-use-equals-terrorism spots) have now been pulled, as my 25-year-old daughter, a graduate of the DARE program, remarked when she heard the recent news about Ecstasy, "Now I'm convinced that any information about drugs coming out of the government is automatically suspect."
The problem, of course, is much bigger than this one piece of research, and is bigger than Ecstasy. It provides just one example of the way in which science is manipulated to promote partisan public policy. That's what the ranking member of the House Committee on Government Reform, Rep. Henry Waxman, D-Calif., learned when he began to investigate the administration's use of scientific information. Regarding more than 20 issues, including substance abuse, his shocking report concludes, "The Bush administration has manipulated, distorted, or interfered with science on health, environmental, and other key issues" (
http://www.house.gov/reform/min/politicsandscience/).
As the mother of a teenager and a young adult, my main concern, like that of most parents, is the safety of my children. It would help if, along with the retraction of the faulty Ecstasy research, the policies that came in its wake -- the RAVE act and the "this is your brain" education campaign -- were retracted as well. Indeed, the National Institute on Drug Abuse Web site has now pulled some of its information on Ecstasy and says it is being revised.
If young Americans are ever to believe what our government tells them about drugs and other policy issues, we must be sure that our messages are based on sound science rather than political ideology. Only then will young people have the kind of trusted information they need to make sound health decisions.
Marsha Rosenbaum directs the Safety First project of the Drug Policy Alliance in San Francisco;
http://www.drugpolicy.org M.v.h
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