Scientists Sharply Criticize Conclusions of New MDMA (Ecstasy) Report
Test Monkeys Injected With Deadly Doses of Drug; Study Did Not Simulate Human Use
Sep 26, 2002
Scientists have expressed strong criticism of a new report about MDMA to be published in the journal Science on September 27. The primate study, by Dr. George Ricaurte and colleagues, reports that MDMA - or Ecstasy - damages dopamine neurons in the brain, and suggests that such damage indicates that MDMA may cause Parkinson's disease in humans.
Critics, pointing to questionable assumptions in Dr. Ricaurte's report, say it suggests no such thing. And they express concern about the hysteria often generated by exaggerated estimates of drug-related harms - which, they say, can hinder the efforts of parents and teachers to establish open, honest dialogue with young people about drug use.
Dr. Juan Sanchez-Ramos, Ellis Professor of Neurology, University of South Florida, and an expert in Parkinson's and dopaminergic neurotoxicity, said, "The multiple dose regimen of injected MDMA administered by Dr. Ricaurte to primates does not simulate human exposure, does not cause cell death, and does not predict anything about human vulnerability to Parkinson's as a result of MDMA. In fact, Dr. Ricaurte's study shows that it is far easier to kill whole animals than to kill neurons."
According to youth drug education experts, it is counterproductive to overstate and misrepresent the harms of drug use. But they say that all too often, research results - and the way they are promoted and used -- are driven more by drug war politics and a scare tactics philosophy than by scientific principle.
"Like everyone, young people stop trusting you when you bend the truth to scare them," said Marsha Rosenbaum, director of the Safety First Project of the Drug Policy Alliance. "Good science, not misguided fear, is what helps us talk honestly and effectively with our teenagers about drug use and their safety."
Scientists pointed to several important flaws in the Science report:
1) The doses administered are not representative of human doses
The paper's prepublication title, "Severe Dopaminergic Neurotoxicity in Primates after a Single Recreational Dose Regime of MDMA (Ecstasy)," suggests it provides evidence about the effects of a single recreational dose of MDMA. In fact, however, all but two of the primates in the study were actually injected with three doses of MDMA within a 6-hour period. This multiple dosage regime killed 20% of the animals (2 out of 10), and possibly would have killed another 20% except for the fact that signs of distress caused the researchers not to administer the third injection.
Dr. Ricaurte and colleagues claim that according to their interspecies scaling model, which they use to estimate the human equivalents of the doses administered to animals, "individual doses of MDMA administered in this study are lower than those typically used by humansS" It is difficult to believe, say critics, that a dose regimen this fatal is equivalent to amounts commonly self-administered by humans, in which fatal reactions are exceptionally rare. Critics say this difference in lethality further calls into question the validity of the interspecies scaling model used by Dr. Ricaurte and colleagues.
2) Data from actual human studies shows no dopamine reductions from MDMA
Dr. Ricaurte and colleagues suggest that individuals taking MDMA may have analogous dopamine changes with increased risk of Parkinson's Disease. However, they failed to cite several recent human brain scan studies and a post-mortem autopsy study that found normal dopamine systems in very experienced illicit MDMA users. These human studies suggest that MDMA may not result in dopamine changes in humans.
Dr. Ricaurte and colleagues have themselves carried out human spinal tap studies in very experienced MDMA users and found no evidence to indicate lowered dopamine metabolites. These spinal tap studies, also not cited in the Science article, are an indirect measure of possible Parkinson's risk and have been superseded by more accurate brain scan and autopsy studies.
3) There is no proven link between Parkinson's and amphetamine or methamphetamine
The dopamine changes produced by MDMA in this study are similar to those caused by d-amphetamine and d-methamphetamine, two drugs legally available as prescription medicines at present and for more than half a century. During that time there has been no convincing evidence linking these dopamine changes to Parkinson's Disease. This suggests that more evidence is needed before linking the dopaminergic changes produced by Dr Ricaurte's multiple dose regime to neurological disease in humans.
Risk/Benefit Analysis for MDMA/PTSD Psychotherapy Research
The FDA has approved a study into the use of MDMA-assisted psychotherapy in the treatment of patients with posttraumatic stress disorder (PTSD). Patients must have failed to obtain relief from at least one course of treatment with a serotonin-selective reuptake inhibitor (SSRI), such as Zoloft, Paxil or Prozac, the only type of medicine FDA-approved for PTSD. This study will involve two oral administrations, three to five weeks apart, of a single dose of 125 mgs of MDMA in an air-conditioned room with subjects reclining on a couch and drinking an adequate amount of fluids. According to Rick Doblin, Ph.D., President of the Multidisciplinary Association for Psychedelic Studies (MAPS, www.maps.org), the non-profit organization that is sponsoring the MDMA/PTSD study, "It has taken 17 years since MDMA was made illegal in 1985 before a double-blind, placebo-controlled study of the therapeutic use of MDMA has been approved by the FDA. During that time, over 260 people worldwide have already been administered MDMA in clinical research studies focused on evaluating various aspects of the safety of MDMA, without demonstrating evidence of harm to those human subjects. Dr. Ricaurte's latest findings do not significantly change the risk/benefit ratio for the subjects who will volunteer for our study. MDMA/PTSD research remains scientifically and ethically justified."
For additional information, contact:
Juan Sanchez-Ramos, PhD, MD
expert in Parkinson's and in dopaminergic neurotoxicity.
Ellis Professor of Neurology
University of South Florida
12901 Bruce B Downs Blvd (MDC 55)
Tampa, FL 33620
Academic Office phone: 813-974-5841 or 6022
office FAX: 813-974-7200; jsramos@hsc.usf.edu
Dr. Jim O'Callaghan, Chief, Molecular Neurotoxicology
Lab, Center for
Disease
Control. jdo5@cdc.gov
NOTE: Dr. O'Callaghan can answer questions about neurotoxicity but any quotes attributed to him need to be cleared by Fred Blosser, Public Affairs Officer, CDC-NIOSH 202-401-3749 FBlosser@cdc.gov.
Rick Doblin, Ph.D.
President, Multidisciplinary Association for Psychedelic Studies (MAPS)
617 484-8711
rick@maps.org
www.maps.org
Marsha Rosenbaum, Ph.D.
Director, Safety First Project, Drug Policy Alliance
415-982-3277
Critics, pointing to questionable assumptions in Dr. Ricaurte's report, say it suggests no such thing. And they express concern about the hysteria often generated by exaggerated estimates of drug-related harms - which, they say, can hinder the efforts of parents and teachers to establish open, honest dialogue with young people about drug use.
Dr. Juan Sanchez-Ramos, Ellis Professor of Neurology, University of South Florida, and an expert in Parkinson's and dopaminergic neurotoxicity, said, "The multiple dose regimen of injected MDMA administered by Dr. Ricaurte to primates does not simulate human exposure, does not cause cell death, and does not predict anything about human vulnerability to Parkinson's as a result of MDMA. In fact, Dr. Ricaurte's study shows that it is far easier to kill whole animals than to kill neurons."
According to youth drug education experts, it is counterproductive to overstate and misrepresent the harms of drug use. But they say that all too often, research results - and the way they are promoted and used -- are driven more by drug war politics and a scare tactics philosophy than by scientific principle.
"Like everyone, young people stop trusting you when you bend the truth to scare them," said Marsha Rosenbaum, director of the Safety First Project of the Drug Policy Alliance. "Good science, not misguided fear, is what helps us talk honestly and effectively with our teenagers about drug use and their safety."
Scientists pointed to several important flaws in the Science report:
1) The doses administered are not representative of human doses
The paper's prepublication title, "Severe Dopaminergic Neurotoxicity in Primates after a Single Recreational Dose Regime of MDMA (Ecstasy)," suggests it provides evidence about the effects of a single recreational dose of MDMA. In fact, however, all but two of the primates in the study were actually injected with three doses of MDMA within a 6-hour period. This multiple dosage regime killed 20% of the animals (2 out of 10), and possibly would have killed another 20% except for the fact that signs of distress caused the researchers not to administer the third injection.
Dr. Ricaurte and colleagues claim that according to their interspecies scaling model, which they use to estimate the human equivalents of the doses administered to animals, "individual doses of MDMA administered in this study are lower than those typically used by humansS" It is difficult to believe, say critics, that a dose regimen this fatal is equivalent to amounts commonly self-administered by humans, in which fatal reactions are exceptionally rare. Critics say this difference in lethality further calls into question the validity of the interspecies scaling model used by Dr. Ricaurte and colleagues.
2) Data from actual human studies shows no dopamine reductions from MDMA
Dr. Ricaurte and colleagues suggest that individuals taking MDMA may have analogous dopamine changes with increased risk of Parkinson's Disease. However, they failed to cite several recent human brain scan studies and a post-mortem autopsy study that found normal dopamine systems in very experienced illicit MDMA users. These human studies suggest that MDMA may not result in dopamine changes in humans.
Dr. Ricaurte and colleagues have themselves carried out human spinal tap studies in very experienced MDMA users and found no evidence to indicate lowered dopamine metabolites. These spinal tap studies, also not cited in the Science article, are an indirect measure of possible Parkinson's risk and have been superseded by more accurate brain scan and autopsy studies.
3) There is no proven link between Parkinson's and amphetamine or methamphetamine
The dopamine changes produced by MDMA in this study are similar to those caused by d-amphetamine and d-methamphetamine, two drugs legally available as prescription medicines at present and for more than half a century. During that time there has been no convincing evidence linking these dopamine changes to Parkinson's Disease. This suggests that more evidence is needed before linking the dopaminergic changes produced by Dr Ricaurte's multiple dose regime to neurological disease in humans.
Risk/Benefit Analysis for MDMA/PTSD Psychotherapy Research
The FDA has approved a study into the use of MDMA-assisted psychotherapy in the treatment of patients with posttraumatic stress disorder (PTSD). Patients must have failed to obtain relief from at least one course of treatment with a serotonin-selective reuptake inhibitor (SSRI), such as Zoloft, Paxil or Prozac, the only type of medicine FDA-approved for PTSD. This study will involve two oral administrations, three to five weeks apart, of a single dose of 125 mgs of MDMA in an air-conditioned room with subjects reclining on a couch and drinking an adequate amount of fluids. According to Rick Doblin, Ph.D., President of the Multidisciplinary Association for Psychedelic Studies (MAPS, www.maps.org), the non-profit organization that is sponsoring the MDMA/PTSD study, "It has taken 17 years since MDMA was made illegal in 1985 before a double-blind, placebo-controlled study of the therapeutic use of MDMA has been approved by the FDA. During that time, over 260 people worldwide have already been administered MDMA in clinical research studies focused on evaluating various aspects of the safety of MDMA, without demonstrating evidence of harm to those human subjects. Dr. Ricaurte's latest findings do not significantly change the risk/benefit ratio for the subjects who will volunteer for our study. MDMA/PTSD research remains scientifically and ethically justified."
For additional information, contact:
Juan Sanchez-Ramos, PhD, MD
expert in Parkinson's and in dopaminergic neurotoxicity.
Ellis Professor of Neurology
University of South Florida
12901 Bruce B Downs Blvd (MDC 55)
Tampa, FL 33620
Academic Office phone: 813-974-5841 or 6022
office FAX: 813-974-7200; jsramos@hsc.usf.edu
Dr. Jim O'Callaghan, Chief, Molecular Neurotoxicology
Lab, Center for
Disease
Control. jdo5@cdc.gov
NOTE: Dr. O'Callaghan can answer questions about neurotoxicity but any quotes attributed to him need to be cleared by Fred Blosser, Public Affairs Officer, CDC-NIOSH 202-401-3749 FBlosser@cdc.gov.
Rick Doblin, Ph.D.
President, Multidisciplinary Association for Psychedelic Studies (MAPS)
617 484-8711
rick@maps.org
www.maps.org
Marsha Rosenbaum, Ph.D.
Director, Safety First Project, Drug Policy Alliance
415-982-3277