MAPS: FW: NEJM article on "Ecstasy"

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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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