Major Error in Ecstasy Research
Ricaurte's Team Accidentally Gave Monkeys Methamphetamine instead of MDMA
v1.0 - Sep 2003
In September 2002, a Johns Hopkins research team (led by George Ricaurte) published new research results in a controversial paper in Science titled Severe Dopaminergic Neurotoxicity in Primates After a Common Recreational Dose Regimen of MDMA. They reported that MDMA, when injected into non-human primates (monkeys) in doses similar to those used by some recreational ecstasy users, caused "severe" damage to the dopamine (DA) system of the brain. But in a major blow to their credibility, the Johns Hopkins researchers have now issued a full retraction of the article stating that all but one of the monkeys were accidentally injected with methamphetamine, not MDMA.
The original article stirred controversy for several reasons. The alarming results, which contradicted previous research and data about actual human use, suggested that even a single evening of MDMA use could lead to permanent and devastating problems. Despite the unexpected results, the Science article was worded to have a political effect and was used to help push through legislation aimed at punishing owners of venues where drugs such as ecstasy are used. The research was strongly supported by Alan Leshner, the former head of the National Institute on Drug Abuse (NIDA). Leshner was head of NIDA when the Johns Hopkins research proposal was approved, and was then appointed chief executive officer of the organization that publishes Science prior to the research being accepted for publication.
As critics have questioned the results over the past year, the authors have vigorously defended their unprecedented findings. But in early September 2003, Ricaurte and his research team submitted a full retraction of the article to Science, stating that the monkeys had not been injected with MDMA at all. Rather, they had been injected with methamphetamine, a well-known dopamine system toxin taken at doses substantially lower than those of MDMA. The results, after injecting the monkeys with what turned out to be very high doses of methamphetamine, were dramatic but not unexpected given the actual substance used: two of the primates died from the injection, others were close to death, and there was serious damage to their dopamine systems.
This retraction highlights some troubling questions about the politics of science and its effect on the data that make it into peer reviewed literature.
Rick Doblin and the team at MAPS are following this issue closely and keeping a list of news articles and responses at: http://www.maps.org/research/mdma/studyresponse.html. Some of these articles are listed below.
Related Documents
News Stories & Commentary
Audio / Video
18 September 2003 Volume 425 Issue no 6955
Ecstasy's after-effect
Following the retraction of a high-profile paper, the US research agency that supports research on drug abuse needs to ensure its independence from intense political pressure to prove that recreational drugs are harmful.
It was a pretty peculiar result in the first place.Neuroscientist George Ricaurte and colleagues at the Johns Hopkins School of Medicine in Baltimore,Maryland, reported that they had injected monkeys and baboons with the equivalent of three recreational hits of ecstasy, with shocking consequences. Two of the ten animals died, and nearly all the rest had damage to neurons involved in movement and mood.
It turns out that the researchers had injected the animals with methamphetamine â€" commonly known as speed â€" by mistake (see Nature 425, 109; 2003). The team deserves credit for the prompt retraction of its paper in Science. But there remains a bad smell that the American Association for the Advancement of Science (AAAS), which publishes Science, and the National Institute of Drug Abuse (NIDA),which funded the research,have done little to clear up.
The reverberations of the original publication â€" which was subjected to far more US media coverage than this month’s retraction â€" are considerable. The mislabelled bottle that the authors say caused their mistake contained 10 grams of methamphetamine, only about a gram of which was used in that particular study.Ricaurte told Nature that at least one more study will need to be retracted. The rest of the bottle’s contents were used in experiments that are as yet unpublished.
The retracted paper left the public with the impression that ecstasy is far more hazardous than it may actually turn out to be. This perception may have influenced the fate of the Reducing Americans’ Vulnerability to Ecstasy Act. The act, which was appended to another bill and signed into law in April, holds club owners responsible for drug use on their premises. Critics say it is unlikely to reduce ecstasy use, but may discourage club owners from voluntary measures to protect users, such as cool-off rooms for the dangerous overheating that can occur with ecstasy, as these are tantamount to admission that drug use is going on.The legislation might have passed anyway, even if Ricaurte’ s study had never been published, but the news certainly lent it urgency.
The impression that low doses of ecstasy,or MDMA,are extremely dangerous â€" misleadingly borne out by Ricaurte’s study, but not by two decades of observing the drug being used â€" will hamper legitimate research to determine whether MDMA could have useful psychotherapeutic properties.Proponents claim that MDMA can be a powerful adjunct to psychotherapy for conditions such as posttraumatic stress disorder,because it promotes self-awareness.At least three studies of this are now under way in Europe. But funding for such work isn’t forthcoming in the United States, and proponents say that part of the blame rests with Ricaurte’s now-discredited study. Another remarkable aspect of this episode is the public endorsement of the study, at the time of its publication, by Alan Leshner, chief executive of the AAAS and former director of NIDA. It isn’t clear why an officer of the AAAS should be involved at all in publicly promoting a particular result published in its journal, least of all one whose outcome was questioned at the outset by several experts. The AAAS issued the retraction late in the afternoon on Friday 5 September, resulting in low-key media coverage, which contrasts sharply with the hype surrounding the initial paper.
Some observers have in the past questioned NIDA’s ability to maintain its independence in the face of the immense pressures brought to bear by those who stand behind America’s interminable ‘war on drugs’. Now that Leshner is at the AAAS, he needs to safeguard its independence, rather than pander to the Bush administration’s jihad against recreational drug use.It falls to the new director ofNIDA,Nora Volkow, to bolster NIDA’s reputation.She might start with a thorough public review of the circumstances and participants’ roles in one of the more bizarre episodes in the history of drug research.
Nature: Nature 425, 109 (11 September 2003)
Agony for researchers as mix-up forces retraction of ecstasy study
JONATHAN KNIGHT
[SAN FRANCISCO] Drug researchers are this week hitting out at scientists who accidentally injected monkeys with methamphetamine or 'speed' when they were supposed to be studying the effects of the drug ecstasy.
In results published last September, a team at the Johns Hopkins University School of Medicine in Baltimore, Maryland, showed for the first time that repeated small doses of ecstasy damaged brain cells that produce the neurotransmitter dopamine in monkeys (G. A. Ricaurte et al. Science 297, 2260-2263; 2002). Deficiencies in dopamine are linked to neurological disorders including Parkinson's disease. But the researchers will retract their study in this week's issue of Science, after concluding that they injected the wrong drug.
Now critics charge that the team led by George Ricaurte was too eager to publish its high-profile finding in this case.
The original study was accompanied by a blaze of publicity in the United States, where it was widely interpreted as evidence that taking ecstasy can lead to brain damage. Johns Hopkins, the National Institute on Drug Abuse (NIDA) in Bethesda, Maryland, which funded the study, and Science's publisher, the American Association for the Advancement of Science (AAAS), each heavily promoted the result. Unusually, Alan Leshner, chief executive of the AAAS and former director of NIDA, publicly endorsed the study, saying: "It sends an important public-health message don't experiment with your own brain."
In their retraction, the authors say that they have been unable to repeat their results. After months of trying to trace the problem, they concluded that all but one of the monkeys had actually received methamphetamine, a powerful stimulant known to damage dopamine-making cells.
The mix-up occurred before the drugs arrived at the lab, the authors say. Similar quantities of the two drugs were ordered and arrived on the same day, their labels apparently reversed. Although the original vial labelled ecstasy has been discarded, tests on the methamphetamine vial show that it contained pure ecstasy, the retraction says.
But the authors should have been suspicious sooner, says Charles Grob, a psychiatrist at the Harbor-UCLA Medical Center in Los Angeles who studies ecstasy, also known as MDMA. "It was implausible that MDMA could have caused those findings," he says. Critics have argued that the study, in which the injections resulted in the sudden death of two out of ten monkeys, could not be representative of recreational ecstasy use by people.
Grob and other critics have in the past argued that other studies by Ricaurte, drawing on brain scans, were equally inconclusive. "This is part of a pattern in Ricaurte's work," Grob alleges.
John Henry, a psychoactive-drug researcher at Imperial College, London, characterizes the retraction as a carefully worded plea for more money. He points out that the last sentence leaves open the possibility that the basic result is right, despite failed attempts to repeat the experiment. "It's extremely arrogant," he says. Henry claims that NIDA favours studies that are liable to prove the toxicity of recreational drugs.
Ricaurte could not be reached for comment but his wife and co-author, Hopkins researcher Una McCann, defended the basic hypothesis that ecstasy use can cause Parkinson-like symptoms. She says that it is clearly toxic to dopamine cells in mice, for instance. "We thought we were getting the high levels of dopamine toxicity seen in other species," she says.
Michael Taffe, who studies MDMA at the Scripps Research Institute in La Jolla, California, says that it would have been a tough call whether to publish the original paper, given the potential importance of the finding. Nor would anyone normally test the contents of a labelled bottle from a manufacturer: "I don't know what I would have done," he says.
Ricaurte's group ordered the drugs from NIDA, which supplies approved researchers through a contractor, RTI International of Research Triangle Park, North Carolina. RTI said in a statement that it was reviewing procedures, but has no evidence that it had made a mistake.
NIDA associate director Timothy Condon says that NIDA will assist RTI in the review, but that there would be no further investigation of how the mix-up occurred. "We have asked RTI to look at their procedures," he says. "I don't know what else we could do."
But Grob doubts whether there will be a real attempt to get to the bottom of the episode. "I think NIDA needs to answer some questions," he says.
© 2003 Nature Publishing Group
The original article stirred controversy for several reasons. The alarming results, which contradicted previous research and data about actual human use, suggested that even a single evening of MDMA use could lead to permanent and devastating problems. Despite the unexpected results, the Science article was worded to have a political effect and was used to help push through legislation aimed at punishing owners of venues where drugs such as ecstasy are used. The research was strongly supported by Alan Leshner, the former head of the National Institute on Drug Abuse (NIDA). Leshner was head of NIDA when the Johns Hopkins research proposal was approved, and was then appointed chief executive officer of the organization that publishes Science prior to the research being accepted for publication.
As critics have questioned the results over the past year, the authors have vigorously defended their unprecedented findings. But in early September 2003, Ricaurte and his research team submitted a full retraction of the article to Science, stating that the monkeys had not been injected with MDMA at all. Rather, they had been injected with methamphetamine, a well-known dopamine system toxin taken at doses substantially lower than those of MDMA. The results, after injecting the monkeys with what turned out to be very high doses of methamphetamine, were dramatic but not unexpected given the actual substance used: two of the primates died from the injection, others were close to death, and there was serious damage to their dopamine systems.
This retraction highlights some troubling questions about the politics of science and its effect on the data that make it into peer reviewed literature.
Rick Doblin and the team at MAPS are following this issue closely and keeping a list of news articles and responses at: http://www.maps.org/research/mdma/studyresponse.html. Some of these articles are listed below.
Related Documents
News Stories & Commentary
- Ecstasy Agonistes, Feb 27 2004
- Bad Trip on E, Dec 6 2003
- Out of the Club, onto the Couch, Dec 5 2003
- Ecstasy Researcher's Work Questioned, Dec 5 2003
- The Agony of Ecstasy Research, Bailey - Reasononline Dec 3, 2003
- An Ouchie For George, Mark Kleiman Dec 2 2003
- Research on Ecstasy is Clouded by Errors, Dec 2 2003 NYTimes
- RTI Denies Switch was their mistake, Nov 7 2003
- Independent inquiry demanded into Ecstasy affair, The Scientist - Sep 18 2003
- Retracted Ecstasy paper "an outrageous scandal", The Scientist - Sep 16 2003
- It'll kill you -- wait, no it won't, SF Chronicle (Editorial) - Sep 15, 2003
- E-fer Madness, Salon - Sep 15 2003
- Scientists retract second drug study, Sunspot.net - Sep 12, 2003
- Your Brain on Bad Science, LA Weekly - Sep 12 2003
- Scientist: Research Error Undermines Drug Warnings, Reuters - Sep 11 2003
- Withdrawal Symptoms: A controversial paper on the effects of Ecstasy is retracted, fuelling debate, The Economist - Sep 11 2003
- 'Killer' Ecstasy Claim was False, BBC - Sep 8 2003
- Ecstasy study used wrong drug, withdrawn, Washington Times - Sep 8 2003
- Controversial ecstasy research used wrong drug, New Scientist - Sep 8 2003
- Journal retracts study on Ecstasy brain damage, CBC News - Sep 8 2003
- Results Retracted on Ecstasy Study, Washington Post - Sep 8 2003
- Scientists admit: we were wrong about 'E', Guardian UK - Sep 7 2003
- Bottles Mixed up in Ecstasy Study, Wired News - Sep 7 2003
- Report of Ecstasy Drug's Great Risks Is Retracted, New York Times - Sep 7 2003
- RTI says Ricaurte is wrong about mislabelling
Audio / Video
- The Science Show (Australia), Sep 20 2003 (real audio)
18 September 2003 Volume 425 Issue no 6955
Ecstasy's after-effect
Following the retraction of a high-profile paper, the US research agency that supports research on drug abuse needs to ensure its independence from intense political pressure to prove that recreational drugs are harmful.
It was a pretty peculiar result in the first place.Neuroscientist George Ricaurte and colleagues at the Johns Hopkins School of Medicine in Baltimore,Maryland, reported that they had injected monkeys and baboons with the equivalent of three recreational hits of ecstasy, with shocking consequences. Two of the ten animals died, and nearly all the rest had damage to neurons involved in movement and mood.
It turns out that the researchers had injected the animals with methamphetamine â€" commonly known as speed â€" by mistake (see Nature 425, 109; 2003). The team deserves credit for the prompt retraction of its paper in Science. But there remains a bad smell that the American Association for the Advancement of Science (AAAS), which publishes Science, and the National Institute of Drug Abuse (NIDA),which funded the research,have done little to clear up.
The reverberations of the original publication â€" which was subjected to far more US media coverage than this month’s retraction â€" are considerable. The mislabelled bottle that the authors say caused their mistake contained 10 grams of methamphetamine, only about a gram of which was used in that particular study.Ricaurte told Nature that at least one more study will need to be retracted. The rest of the bottle’s contents were used in experiments that are as yet unpublished.
The retracted paper left the public with the impression that ecstasy is far more hazardous than it may actually turn out to be. This perception may have influenced the fate of the Reducing Americans’ Vulnerability to Ecstasy Act. The act, which was appended to another bill and signed into law in April, holds club owners responsible for drug use on their premises. Critics say it is unlikely to reduce ecstasy use, but may discourage club owners from voluntary measures to protect users, such as cool-off rooms for the dangerous overheating that can occur with ecstasy, as these are tantamount to admission that drug use is going on.The legislation might have passed anyway, even if Ricaurte’ s study had never been published, but the news certainly lent it urgency.
The impression that low doses of ecstasy,or MDMA,are extremely dangerous â€" misleadingly borne out by Ricaurte’s study, but not by two decades of observing the drug being used â€" will hamper legitimate research to determine whether MDMA could have useful psychotherapeutic properties.Proponents claim that MDMA can be a powerful adjunct to psychotherapy for conditions such as posttraumatic stress disorder,because it promotes self-awareness.At least three studies of this are now under way in Europe. But funding for such work isn’t forthcoming in the United States, and proponents say that part of the blame rests with Ricaurte’s now-discredited study. Another remarkable aspect of this episode is the public endorsement of the study, at the time of its publication, by Alan Leshner, chief executive of the AAAS and former director of NIDA. It isn’t clear why an officer of the AAAS should be involved at all in publicly promoting a particular result published in its journal, least of all one whose outcome was questioned at the outset by several experts. The AAAS issued the retraction late in the afternoon on Friday 5 September, resulting in low-key media coverage, which contrasts sharply with the hype surrounding the initial paper.
Some observers have in the past questioned NIDA’s ability to maintain its independence in the face of the immense pressures brought to bear by those who stand behind America’s interminable ‘war on drugs’. Now that Leshner is at the AAAS, he needs to safeguard its independence, rather than pander to the Bush administration’s jihad against recreational drug use.It falls to the new director ofNIDA,Nora Volkow, to bolster NIDA’s reputation.She might start with a thorough public review of the circumstances and participants’ roles in one of the more bizarre episodes in the history of drug research.
Nature: Nature 425, 109 (11 September 2003)
Agony for researchers as mix-up forces retraction of ecstasy study
JONATHAN KNIGHT
[SAN FRANCISCO] Drug researchers are this week hitting out at scientists who accidentally injected monkeys with methamphetamine or 'speed' when they were supposed to be studying the effects of the drug ecstasy.
In results published last September, a team at the Johns Hopkins University School of Medicine in Baltimore, Maryland, showed for the first time that repeated small doses of ecstasy damaged brain cells that produce the neurotransmitter dopamine in monkeys (G. A. Ricaurte et al. Science 297, 2260-2263; 2002). Deficiencies in dopamine are linked to neurological disorders including Parkinson's disease. But the researchers will retract their study in this week's issue of Science, after concluding that they injected the wrong drug.
Now critics charge that the team led by George Ricaurte was too eager to publish its high-profile finding in this case.
The original study was accompanied by a blaze of publicity in the United States, where it was widely interpreted as evidence that taking ecstasy can lead to brain damage. Johns Hopkins, the National Institute on Drug Abuse (NIDA) in Bethesda, Maryland, which funded the study, and Science's publisher, the American Association for the Advancement of Science (AAAS), each heavily promoted the result. Unusually, Alan Leshner, chief executive of the AAAS and former director of NIDA, publicly endorsed the study, saying: "It sends an important public-health message don't experiment with your own brain."
In their retraction, the authors say that they have been unable to repeat their results. After months of trying to trace the problem, they concluded that all but one of the monkeys had actually received methamphetamine, a powerful stimulant known to damage dopamine-making cells.
The mix-up occurred before the drugs arrived at the lab, the authors say. Similar quantities of the two drugs were ordered and arrived on the same day, their labels apparently reversed. Although the original vial labelled ecstasy has been discarded, tests on the methamphetamine vial show that it contained pure ecstasy, the retraction says.
But the authors should have been suspicious sooner, says Charles Grob, a psychiatrist at the Harbor-UCLA Medical Center in Los Angeles who studies ecstasy, also known as MDMA. "It was implausible that MDMA could have caused those findings," he says. Critics have argued that the study, in which the injections resulted in the sudden death of two out of ten monkeys, could not be representative of recreational ecstasy use by people.
Grob and other critics have in the past argued that other studies by Ricaurte, drawing on brain scans, were equally inconclusive. "This is part of a pattern in Ricaurte's work," Grob alleges.
John Henry, a psychoactive-drug researcher at Imperial College, London, characterizes the retraction as a carefully worded plea for more money. He points out that the last sentence leaves open the possibility that the basic result is right, despite failed attempts to repeat the experiment. "It's extremely arrogant," he says. Henry claims that NIDA favours studies that are liable to prove the toxicity of recreational drugs.
Ricaurte could not be reached for comment but his wife and co-author, Hopkins researcher Una McCann, defended the basic hypothesis that ecstasy use can cause Parkinson-like symptoms. She says that it is clearly toxic to dopamine cells in mice, for instance. "We thought we were getting the high levels of dopamine toxicity seen in other species," she says.
Michael Taffe, who studies MDMA at the Scripps Research Institute in La Jolla, California, says that it would have been a tough call whether to publish the original paper, given the potential importance of the finding. Nor would anyone normally test the contents of a labelled bottle from a manufacturer: "I don't know what I would have done," he says.
Ricaurte's group ordered the drugs from NIDA, which supplies approved researchers through a contractor, RTI International of Research Triangle Park, North Carolina. RTI said in a statement that it was reviewing procedures, but has no evidence that it had made a mistake.
NIDA associate director Timothy Condon says that NIDA will assist RTI in the review, but that there would be no further investigation of how the mix-up occurred. "We have asked RTI to look at their procedures," he says. "I don't know what else we could do."
But Grob doubts whether there will be a real attempt to get to the bottom of the episode. "I think NIDA needs to answer some questions," he says.
© 2003 Nature Publishing Group
Cartoon Idea: Monkey #1: Dude, how was that E you scored last week? Monkey #2: It was f*cking speed. Again. Monkey #1: Bummer, dude. carter (metafilter.com) sep 2003