Re: MAPS: FW: NEJM article on "Ecstasy"

[Walter Mandell <wmandell@xxxxxxxxxxxxxx>]

I am a retired physician. I'm not defending the report. No generalization
should ever be made for a correlation based on an N of 1, yet that is what the
authors do. Although the authors cite studies of MPTP toxicity, by their own
admission such studies show nigro-striatal damage on PET scan, which this
patient did not show. No chemical analysis of the drug he took was done, so
there is no evidence that the patient was ever exposed to MPTP. Absolutely no
conclusion can be reached as to the cause of his neurological disorder.

That is not to give MDMA a clean bill of health. It is to say that there is no
good evidence that the patient's disease was a result of taking MDMA or any
contaminant contained in the stuff he thought was MDMA. It's possible there
was MPTP present, but it is not proven. It is possible that MDMA itself caused
the problem, but that is not proven either.

I think your conspiracy theory however misses the mark. Drug companies are not
concerned about MDMA. Police are, parents are, religious groups are, the WOD
industry  is. The beneficiaries of the WOD are not the pharmaceutical houses
(except as they are involved in making drug testing kits, or selling methadone
etc., or selling prescription narcotics, benzodiazepines, and stimulants that
will ultimately wind up on the street). The main beneficiaries of the current
drug laws are the legal and law enforcement professions (RICO enables the
police to fund their activities with money and the sale of property
confiscated from drug suspects), the drug rehabilitation industry, the private
prison industry, the various state prison employees, the construction firms
that make money when the states build more prisons, and certainly the drug
testing industry. It should not be forgotten that studies aimed against drugs
abuse will get funded. This will bias what gets reported in even the best of
peer reviewed journals.

walt

maps-forum@xxxxxxxx wrote:

> Mod. Note: so many have forwarded this article to me that I'm starting to
> think it warrants the status of an urban legend that needs to be debunked.
> If you have seen this report before, I urge you to look at the title,
> "Parkinsonism after Taking Ecstacy." This title is misleading because it
> suggests a general phenomenon, whereas this report is only a case study of
> a single subject. Further, we have only this subject's self-report of
> taking something that was sold to him as Ecstacy, whereas some contaminant
> or adulterant is very likely the cause (the authors' own arguments suggest
> that the culprit is MPTP)-- otherwise, we would not have a case report,
> but an epidemiological report of a substantial and consistent number of
> subjects-- or, more likely, we would have seen this result in the animal
> studies many years ago, and MDMA would not be as popular a drug as it is
> today. Nevermind that. Seeing something like this coming out in the New
> England Journal of Medicine is dismaying, and makes me entertain
> conspiracy theories about drug companies worrying about the potential
> impact of MDMA psychotherapy on corporate profits.
>
> Do we have a physician on the list who can defend this publication?
>
> Jon Frederick, M.S.
>
> ------------------------------
> The New England Journal of Medicine -- May 6, 1999 -- Vol. 340,
> No. 18
>
> Parkinsonism after Taking Ecstasy
>
>           To the Editor:
>
> Recreational use of 3,4-methylenedioxymethamphetamine (MDMA,
> or "ecstasy"), a hallucinogen, has increased both in Europe and
> the United States. (1) This substance is manufactured in illicit
> laboratories from a variety of organic ketone precursors. MDMA,
> which is structurally related both to the stimulant amphetamine and
> to the hallucinogen mescaline, promotes the release of both
> serotonin and dopamine from synaptic terminals. (2) We report a
> case of parkinsonism after repeated use of this drug.
>
>  A 29-year-old man had slight clumsiness of his upper and lower
> extremities in August 1998. During the following four weeks he
> began to have difficulty walking and lost the ability to write and to
> drive. He was unable to continue his work in retail merchandising
> and then could not live independently. The results of magnetic
> resonance imaging, electroencephalography, lumbar puncture, and
> positron-emission tomography with [18F]fluorodeoxyglucose were
> normal. Tests for antibodies to the human immunodeficiency virus
> were negative on two occasions. Eleven weeks after the onset of
> symptoms, examination revealed a disturbance in gait and
> impairment of fine coordination. The patient's condition continued to
> worsen, and eight weeks later examination revealed bradykinesia of
> the face and limbs, absence of blinking, hypokinesia in relation to
> speech, postural instability, and a markedly parkinsonian gait.
>
> Cognitive function was normal, and there was no tremor. The
> patient had ingested MDMA nine times in 1997 and once more in
> May 1998. He denied having used any other illicit substances
> except cannabis. Treatment with the maximal tolerated doses of
> levodopa and pramipexole did not improve his symptoms.
>
> Parkinsonism has not previously been associated with the use of
> MDMA. Although we have no firm evidence of a causal relation
> between this patient's drug use and his parkinsonism, there are no
> other tenable explanations.
>
> Idiopathic Parkinson's disease rarely develops in this age group
> and is responsive to medication, and neither it nor parkinsonism of
> any other neurodegenerative cause progresses this rapidly. Our
> patient's condition most closely resembled the parkinsonism
> produced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine, a
> byproduct of the illicit manufacture of meperidine, which is highly
> toxic to neurons of the substantia nigra. Positron-emission
> tomographic studies have shown that even subclinical exposure to
> this substance produces progressive nigrostriatal damage,
> making the subject vulnerable to subsequent parkinsonism. (3)
>
> We hypothesize that our patient may have had parkinsonism as a
> result of a delayed neurotoxic effect of MDMA on the substantia
> nigra and striatum. There is evidence for such dopaminergic
> neurotoxicity in animals, (4,5) and delayed neurotoxicity in humans
> could occur as a result of neuronal damage induced by free
> radicals. (5) Recent research regarding the neurotoxic effects of
> this substance has focused on serotonergic neurotoxicity and
> impairment of memory. (6) This patient's case suggests that the
> effects of MDMA on dopaminergic systems should be studied
> further to characterize more fully the dangers of its use.
>
>           Scott Mintzer, M.D.
>           Susan Hickenbottom, M.D.
>           Sid Gilman, M.D.
>           University of Michigan
>           Ann Arbor, MI 48109
>
>           References
>
> 1. Johnston LD, O'Malley PM, Bachman JG. National survey
> results on drug use from the Monitoring the Future Study, 1975-
> 1995. Vol. 2. College students and young adults. Rockville, Md.:
> National Institutes on Drug Abuse, 1997.
>
> 2. Steele TD, McCann UD, Ricaurte GA. 3,4-
> Methylenedioxymethamphetamine (MDMA, "Ecstasy"):
> pharmacology and toxicology in animals and humans. Addiction
> 1994;89:539-51.
>
> 3. Vingerhoets FJ, Snow BJ, Tetrud JW, Langston JW, Schulzer
> M, Calne DB. Positron emission tomographic evidence for
> progression of human MPTP-induced dopaminergic lesions. Ann
> Neurol 1994;36:765-70.
>
> 4. Obradovic T, Imel KM, White SR. Repeated exposure to
> methylenedioxymethamphetamine (MDMA) alters nucleus
> accumbens neuronal responses to dopamine and serotonin. Brain
> Res 1998;785:1-9.
>
> 5. Seiden LS, Sabol KE. Methamphetamine and
> methylenedioxymethamphetamine neurotoxicity: possible
> mechanisms of cell destruction. In: Majewska MD, ed.
> Neurotoxicity and neuropathology associated with cocaine
> abuse. NIDA research monograph 163. Washington, D.C.:
> Government Printing Office, 1996. (DHHS publication no. (ADM) 96-
> 4019.)
> ------------------------------------------------------------------------
>
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