Retracted article on dopaminergic neurotoxicity of MDMA

Last updated

"Severe dopaminergic neurotoxicity in primates after a common recreational dose regimen of MDMA [nb 1] ("ecstasy")", [1] is an article by George A. Ricaurte that was published in September 2002 in the peer-reviewed journal Science , one of the world's top academic journals. It was later retracted; instead of using MDMA, methamphetamine had been used in the test. [2]

Contents

Original publication

An editorial article on the paper indicated that researchers had observed dopaminergic neurotoxicity (death of neurons involved in dopamine pathways) in monkeys following MDMA injections, a finding which suggested that recreational users of MDMA may be at risk of developing neuropsychiatric disorders associated with dopamine dysfunction. [3]

Following the release of the paper, Science published a “News of the week” article by Constance Holden. [4] The article noted that the results of the study had caused the researchers concern that even a single night of MDMA usage could cause brain damage, and leave a person vulnerable to neurological disorders such as Parkinson's disease. Holden also noted that the findings of the study were surprising, due to MDMA being known for prompting the release of large amounts of serotonin, but not dopamine. In the article, cognitive neuroscientist Jon Cole was described as being “skeptical” about the risk of Parkinson’s from MDMA use, stating that there had only been one case report of Parkinson’s related to the use of ecstasy. In response, the researchers stated that this could be due to symptoms not presenting until "70% to 80%" of dopamine had been depleted.

Alan Leshner, a former director of the National Institute on Drug Abuse, also commented on the study, stating "This says even a single evening's use is playing Russian roulette with your own brain." [5]

Retraction

In June 2003, a letter to Science was published in which the results of the study were questioned. Ricaurte stood by the findings. [6]

In September 2003, the paper was retracted. In a statement published in ‘’Science’’, the research team indicated that due to a labelling error, methamphetamine had been administered to 9 of the 10 test animals instead of MDMA. The team had consistently been unable to replicate the original results, which lead to them conducting an investigation and ultimately discovering the error. [2]

Following the retraction, Ricaurte stated that he would continue to investigate the possibility of a relationship between MDMA and dopamine dysfunction, and that the laboratory would be adjusting its chemical handling procedure. [7]

Reactions

In a review of the year's events published in the December issue of Science, Editor-in-Chief Donald Kennedy wrote, "It was also a vintage year for scientific fluffs. We shared in one: Some vials containing the recreational drug Ecstasy got switched with vials containing methamphetamine, and we wound up publishing a paper we wish we hadn't". [8]

Journalists such as Larry Smith and Carla Spartos have stated that the inaccurate study may have influenced drug policy being made at the time, such as the RAVE act of April 2003. [9] [10] [11]

In an interview in The Scientist, British scientists Colin Blakemore and Leslie Iversen described how they expressed concerns about the article with editors at Science. "It's an outrageous scandal," Iversen told The Scientist. "It's another example of a certain breed of scientist who appear to do research on illegal drugs mainly to show what the governments want them to show. They extract large amounts of grant money from the government to do this sort of biased work." [12]

A study [13] of the 50 largest American newspapers with available online archives found that 26 (52%) covered the original article's publication, while 20 (40%) covered its retraction. Of the newspapers that covered the article's publication, only 14 (54%) covered its retraction, suggesting large numbers of newspaper readers who had been exposed to the misinformation were never made aware that the study had been in error.

See also

Notes

  1. ↑ 3,4-methylenedioxy-N-methylamphetamine (MDMA) is the chemical name for the psychotropic drug commonly known as "ecstasy".

Related Research Articles

<span class="mw-page-title-main">MDMA</span> Psychoactive drug, often called ecstasy

3,4-Methyl​enedioxy​methamphetamine (MDMA), commonly known as ecstasy, and molly or mandy, is a potent empathogen–entactogen with stimulant and minor psychedelic properties. Investigational indications include as an adjunct to psychotherapy in the treatment of post-traumatic stress disorder (PTSD) and social anxiety in autism spectrum disorder. The purported pharmacological effects that may be prosocial include altered sensations, increased energy, empathy, and pleasure. When taken by mouth, effects begin in 30 to 45 minutes and last three to six hours.

<span class="mw-page-title-main">Substantia nigra</span> Structure in the basal ganglia of the brain

The substantia nigra (SN) is a basal ganglia structure located in the midbrain that plays an important role in reward and movement. Substantia nigra is Latin for "black substance", reflecting the fact that parts of the substantia nigra appear darker than neighboring areas due to high levels of neuromelanin in dopaminergic neurons. Parkinson's disease is characterized by the loss of dopaminergic neurons in the substantia nigra pars compacta.

<span class="mw-page-title-main">MPTP</span> Chemical compound

MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine) is an organic compound. It is classified as a tetrahydropyridine. It is of interest as a precursor to the neurotoxin MPP+, which causes permanent symptoms of Parkinson's disease by destroying dopaminergic neurons in the substantia nigra of the brain. It has been used to study disease models in various animals.

In academic publishing, a retraction is a mechanism by which a published paper in an academic journal is flagged for being seriously flawed to the extent that their results and conclusions can no longer be relied upon. Retracted articles are not removed from the published literature but marked as retracted. In some cases it may be necessary to remove an article from publication, such as when the article is clearly defamatory, violates personal privacy, is the subject of a court order, or might pose a serious health risk to the general public.

<span class="mw-page-title-main">3,4-Methylenedioxyamphetamine</span> Empathogen-entactogen, psychostimulant, and psychedelic drug of the amphetamine family

3,4-Methylenedioxyamphetamine is an empathogen-entactogen, psychostimulant, and psychedelic drug of the amphetamine family that is encountered mainly as a recreational drug. In its pharmacology, MDA is a serotonin–norepinephrine–dopamine releasing agent (SNDRA). In most countries, the drug is a controlled substance and its possession and sale are illegal.

<span class="mw-page-title-main">National Institute on Drug Abuse</span> Branch of the National Institutes of Health in the United States

The National Institute on Drug Abuse (NIDA) is a United States federal government research institute whose mission is to "advance science on the causes and consequences of drug use and addiction and to apply that knowledge to improve individual and public health."

George A. Ricaurte is a neurologist and researcher who works at the Johns Hopkins School of Medicine in the Department of Neurology.

<span class="mw-page-title-main">Dopaminergic</span> Substance related to dopamine functions

Dopaminergic means "related to dopamine" (literally, "working on dopamine"), dopamine being a common neurotransmitter. Dopaminergic substances or actions increase dopamine-related activity in the brain. Dopaminergic brain pathways facilitate dopamine-related activity. For example, certain proteins such as the dopamine transporter (DAT), vesicular monoamine transporter 2 (VMAT2), and dopamine receptors can be classified as dopaminergic, and neurons that synthesize or contain dopamine and synapses with dopamine receptors in them may also be labeled as dopaminergic. Enzymes that regulate the biosynthesis or metabolism of dopamine such as aromatic L-amino acid decarboxylase or DOPA decarboxylase, monoamine oxidase (MAO), and catechol O-methyl transferase (COMT) may be referred to as dopaminergic as well. Also, any endogenous or exogenous chemical substance that acts to affect dopamine receptors or dopamine release through indirect actions (for example, on neurons that synapse onto neurons that release dopamine or express dopamine receptors) can also be said to have dopaminergic effects, two prominent examples being opioids, which enhance dopamine release indirectly in the reward pathways, and some substituted amphetamines, which enhance dopamine release directly by binding to and inhibiting VMAT2.

<span class="mw-page-title-main">4-Methylaminorex</span> Group of stereoisomers

4-Methylaminorex is a stimulant drug of the 2-amino-5-aryloxazoline class that was first synthesized in 1960 by McNeil Laboratories. It is also known by its street name "U4Euh" ("Euphoria"). It is banned in many countries as a stimulant.

Sex and drugs date back to ancient humans and have been interlocked throughout human history. Both legal and illegal, the consumption of drugs and their effects on the human body encompasses all aspects of sex, including desire, performance, pleasure, conception, gestation, and disease.

<span class="mw-page-title-main">Dimethylamphetamine</span> Chemical compound

Dimethylamphetamine (Metrotonin), also known as dimetamfetamine (INN), dimephenopan and N,N-dimethylamphetamine, is a stimulant drug of the phenethylamine and amphetamine chemical classes. Dimethylamphetamine has weaker stimulant effects than amphetamine or methamphetamine and is considerably less addictive and less neurotoxic compared to methamphetamine. However, it still retains some mild stimulant effects and abuse potential, and is a Schedule I controlled drug.

<i>para</i>-Chloroamphetamine Chemical compound

para-Chloroamphetamine (PCA), also known as 4-chloroamphetamine (4-CA), is a substituted amphetamine and monoamine releaser similar to MDMA, but with substantially higher neurotoxicity, thought to be due to the unrestrained release of both serotonin and dopamine by a metabolite. It is used as a neurotoxin by neurobiologists to selectively kill serotonergic neurons for research purposes, in the same way that 6-hydroxydopamine is used to kill dopaminergic neurons.

<span class="mw-page-title-main">MDAI</span> Chemical compound

MDAI (5,6-methylenedioxy-2-aminoindane) is a drug developed in the 1990s by a team led by David E. Nichols at Purdue University. It acts as a non-neurotoxic and highly selective serotonin releasing agent (SSRA) in vitro and produces entactogen effects in humans.

<span class="mw-page-title-main">Monoamine releasing agent</span> Class of compounds

A monoamine releasing agent (MRA), or simply monoamine releaser, is a drug that induces the release of a monoamine neurotransmitter from the presynaptic neuron into the synapse, leading to an increase in the extracellular concentrations of the neurotransmitter. Many drugs induce their effects in the body and/or brain via the release of monoamine neurotransmitters, e.g., trace amines, many substituted amphetamines, and related compounds.

A dopamine releasing agent (DRA) is a type of drug which induces the release of dopamine in the body and/or brain. No selective and robust DRAs are currently known. On the other hand, many releasing agents of both dopamine and norepinephrine and of serotonin, norepinephrine, and dopamine are known. Serotonin–dopamine releasing agents (SDRAs), for instance 5-chloro-αMT, are much more rare and are not selective for dopamine release but have also been developed. Examples of major NDRAs include the psychostimulants amphetamine and methamphetamine, while an example of an SNDRA is the entactogen methylenedioxymethamphetamine (MDMA). These drugs are frequently used for recreational purposes and encountered as drugs of abuse. Selective DRAs, as well as NDRAs, have medical applications in the treatment of attention deficit hyperactivity disorder (ADHD).

α-Methyldopamine Chemical compound

α-Methyldopamine (α-Me-DA), also known as 3,4-dihydroxyamphetamine, is a research chemical of the catecholamine and amphetamine chemical classes. Its bis-glutathionyl metabolite is slightly neurotoxic when directly injected into the brain's ventricles.

<span class="mw-page-title-main">UWA-101</span> Chemical compound

UWA-101 is a phenethylamine derivative researched as a potential treatment for Parkinson's disease. Its chemical structure is very similar to that of the illegal drug MDMA, the only difference being the replacement of the α-methyl group with an α-cyclopropyl group. MDMA has been found in animal studies and reported in unauthorised human self-experiments to be effective in the short-term relief of side-effects of Parkinson's disease therapy, most notably levodopa-induced dyskinesia. However the illegal status of MDMA and concerns about its potential for recreational use, neurotoxicity and potentially dangerous side effects mean that it is unlikely to be investigated for medical use in this application, and so alternative analogues were investigated.

<span class="mw-page-title-main">5-MAPB</span> Chemical compound

5-MAPB is an entactogenic designer drug similar to MDMA in its structure and effects.

<span class="mw-page-title-main">Role of serotonin in visual orientation processing</span>

Serotonin (5-hydroxytryptamine) is a monoamine neurotransmitter that plays a role in mood, eating, sleeping, arousal and potentially visual orientation processing. To investigate its function in visual orientation, researchers have utilised MDMA, or as it is commonly referred to, Ecstasy (3,4-methylenedioxymethamphetamine). MDMA is known to affect serotonin neurons in the brain and cause neurotoxicity. Serotonin has been hypothesised to be involved in visual orientation because individuals who use MDMA exhibit an increase in the magnitude of the tilt aftereffect (TAE). The TAE is a visual illusion where viewing lines in one direction, for an extended period of time, produces the perception of a tilt in the opposite direction to vertical lines subsequently viewed. This effect is proposed to occur due to lateral inhibition to orientation sensitive neurons in the occipital lobe. Lateral inhibition is where neurons that become activated to a particular orientation send inhibitory signals to their neighbouring neurons. The degree of orientation that each neuron becomes maximally excited to is referred to as the tuning bandwidth. Lateral inhibition consequently plays a pivotal role in each neuron's tuning bandwidth, such that if lateral inhibition no longer occurs, a greater number of neurons will become stimulated to the same orientation. This results in the activated neurons becoming adapted to the same orientation stimulus, if the stimulus is viewed for a period of time. As a consequence, if those neurons are subsequently 'shown' another stimulus that differs slightly in its orientation, those neurons are no longer able to achieve the same level of response as compared to other non-adapted neurons.

Una D. McCann is a board certified psychiatrist and researcher at Johns Hopkins School of Medicine in the Department of Psychiatry. She is also the Director of the Anxiety Disorders Program, and Co-Director of the Center for Interdisciplinary Sleep Medicine and Research, and Associate Program Director at the Johns Hopkins Bayview Medical Center. McCann is considered to be an expert in anxiety and stress disorders and her primary areas research revolves around amphetamine-induced monoamine neurotoxicity and neurobiology of anxiety disorders.

References

  1. ↑ Ricaurte GA, Yuan J, Hatzidimitriou G, Cord BJ, McCann UD (September 2002). "Severe dopaminergic neurotoxicity in primates after a common recreational dose regimen of MDMA ("ecstasy")". Science. 297 (5590): 2260–3. Bibcode:2002Sci...297.2260R. doi:10.1126/science.1074501. PMID   12351788. S2CID   41968301. (Retracted, see doi:10.1126/science.301.5639.1479b, PMID   12970544)
  2. 1 2 Ricaurte GA, Yuan J, Hatzidimitriou G, Cord BJ, McCann UD (September 2003). "Retraction". Science. 301 (5639): 1479b–1479. doi:10.1126/science.301.5639.1479b. PMID   12970544. S2CID   220097819.
  3. ↑ "More Dangers from Designer Drugs". Science's STKE. 2002 (152): 360tw–360. 2002. doi:10.1126/stke.2002.152.tw360. ISSN   1525-8882. S2CID   219191294.
  4. ↑ "Drug Find Could Give Ravers the Jitters". www.science.org. Retrieved 2021-11-13.
  5. ↑ Rick Weiss "On Ecstasy, Consensus Is Elusive:Study Suggesting Risk of Brain Damage Questioned by Critics of Methodology" Washington Post, September 30, 2002; Page A07. Archived copy
  6. ↑ Mithoefer, Michael; Jerome, Lisa; Doblin, Richard; Ricaurte, George A. (2003-06-06). "MDMA ("Ecstasy") and Neurotoxicity". Science. 300 (5625): 1504–1505. doi:10.1126/science.300.5625.1504. PMID   12791964. S2CID   38721229.
  7. ↑ Holden C (September 2003). "Retraction. Paper on toxic party drug is pulled over vial mix-up". Science. 301 (5639): 1454b–1454. doi:10.1126/science.301.5639.1454b. PMID   12970527. S2CID   36895308.
  8. ↑ Kennedy D (December 2003). "Breakthrough of the year". Science. 302 (5653): 2033. doi:10.1126/science.302.5653.2033. PMID   14684786. S2CID   31164282.
  9. ↑ Smith L (17 September 2003). Richmond C, Talbot D, Keane E (eds.). "E-fer madness". Salon.com . San Francisco, California, United States of America: Salon.com, LLC. OCLC   43916723. Archived from the original on 8 October 2011. Retrieved 10 July 2021.
  10. ↑ Carla Spartos (Mar 2, 2004). "The Ecstasy Factor: Bad Science Slandered a Generation's Favorite Drug. Now a New Study Aims to Undo the Damage". villagevoice. Archived from the original on 2012-10-11. Retrieved 2012-12-14.
  11. ↑ "Ecstasy's after-effects". Nature. 425 (6955): 223. September 2003. Bibcode:2003Natur.425Q.223.. doi: 10.1038/425223a . PMID   13679872.
  12. ↑ "Retracted Ecstasy paper "an outrageous scandal"". The Scientist. 15 September 2003. Retrieved 23 April 2022.
  13. ↑ Barnett, Brian S.; Doblin, Richard (2021). "Dissemination of Erroneous Research Findings and Subsequent Retraction in High-Circulation Newspapers: A Case Study of Alleged MDMA-Induced Dopaminergic Neurotoxicity in Primates". Journal of Psychoactive Drugs. 53 (2): 104–110. doi:10.1080/02791072.2020.1847365. ISSN   2159-9777. PMID   33241981. S2CID   227176796.
This page is based on this Wikipedia article
Text is available under the CC BY-SA 4.0 license; additional terms may apply.
Images, videos and audio are available under their respective licenses.