MAPS: More on NEJM letter

[RickMAPS@xxxxxxx]

To All:

The letter in the NEJM has been hotly debated.  I've just learned it contains 
a crucial mistake. The letter references an animal study by Lew Seiden  that 
supposedly showed MDMA linked to dopamine neurotoxicity. However, the study 
does not show that. The study actually showed the opposite, that MDMA was NOT 
linked to dopamine neurotoxicity.  I am forwarding  a  slightly upset e-mail 
message I received from Dr. Jessica Malberg. She is doing research at Yale 
and earned her Ph.D. working in Dr. Seiden's lab working on the contributing 
role of heat in MDMA neurotoxicity. Here is what Jessica had to say about the 
NEJM letter:

" Never have I seen such a blatant misrepresentation of scientific
data. The fact that it was published disturbs me greatly;   "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."  Um, hello?
No other explanation?  Yeah, right!!!!  Why don't we blame the car --
"after the purchase of the car, he displayed PD-like symptoms.."

But seriously, I see a number of major scientific problems in this article.

	First of all, I may personally contact the authors and ask them to
point out the reference in Seiden and Sabol where it states that MDMA is
neurotoxic to the DA system.  I have a feeling that the authors figured
that Lew's sentences in the intro to that paper that "Meth and other
substituted amphetamines may affect the DA system" also applied to MDMA.
However, if the authors had bothered to read any section specifically
pertaining to MDMA, they would see that indeed, Lew's lab has never
associated MDMA with decreased DA, DOPAC or HVA levels.

	Second is the sweeping assumption that the MDMA use "caused" this
problem. I have rarely seen ANY disease state (at least when first written
about in a journal) that can be attributed taking ONE drug.  Often it is,
"X disease MAY BE caused by use of ---".  The fact that this article was
allowed to be published with this damning title points to a major political
bias, with little regard for the scientific merit.   The authors clearly
wanted to BLAME the drug and our politicial climate and the editorial board
allowed them to do so.

This "blame the MDMA" leads to another point. If you read the 5th paragraph
carefully, it actually says that there is NOT a link between MDMA and
idiopathic Parkinsonism.  The authors state that PD is not usually seen in
this age group and the person did not respond to treatment usually used
with PD.  This paragraph states that there IS, however, a link between MDMA
and Parkinsonian-like symptoms that have been previously observed with MPTP
use.
In my notes, I broke down that 5th paragraph in this way

1) The man took MDMA
2) He reported Parkinson-like symptoms
3) NO PD treatments helped and he did not fit the profile for PD

I would think this would lead most MD's to look for another explanation.

4) His symptoms resembled those of patients who took MPTP.
5) The MPTP users were of a similar age
6) MPTP neurotoxicity has been shown to affect the SN, which could account
for these symptoms [what is NOT stated is that MDMA neurotoxicity has NOT
been shown to affect the DA system (as you stated in a previous post, not
even not even Dr. Ricuarte states that MDMA is neurotoxic to DA!!).]

These statements lead to me, at least, to the conclusion that the man
probably took MPTP!!!

The article does not state if the MDMA was pure, or even from a reliable
source.  As we on the board all know, being TOLD something is MDMA does NOT
make it so!!!! The fact that this article does not even SUGGEST this
possbility makes me see red;  I just wonder how much this article will
affect funding as well as public perception of the drug.  We FINALLY have
scientists publicly agreeing on the need for more research and then an
article like this is published.  Yes, the authors do state that this is a
need for this research, but clearly the research that they envision is
biased towards "studies to further characterize the dangers of [MDMA] use."
The fact that the last sentence was allowed to be published makes me once
again wonder just how biased the editors of NEJM are!!!!


The last paragraph is also full of unsupported statements.  The
neurotoxicity they speak of in the first two sentences (DA neurotoxicity in
the SN and striatum) has NOT BEEN SHOWN.  The recent human studies on 5HT
and impairment are NOT related to DA;  nor have there been any
studies to suggest this.

I would again submit that this article could rightly conclude that the
patient took tainted MDMA or more likely, not MDMA at all.

Therefore,
Why was this article not called something like, "MPTP-like symptoms
reported with MDMA use"
or
"Possbility of MPTP sold as MDMA"

or better, an alert to the CDC or NIDA, not a NEJM article, that
MPTP-symptoms may be crop up in people that think that they have taken MDMA!"

As you can see from Jessica's e-mail message ,  the citation that supposedly 
showed evidence that MDMA causes dopamine neurotoxicity actually showed the 
opposite.   I just went to the library to get the second publication cited by 
the authors of the NEJM letter as support for MDMA dopaminergic 
neurotoxicity. The paper discusses  "blunted inhibitory effects of  DA 
(dopamine) and the D1 receptor agonist on glutamate-evoked firing in the 
MDMA-pretreated animals" in the nucleus accumbens.  In the discussion section 
(perhaps the authors of the letter didn't read this far), we are told that 
"the change in sensitivity to DA CANNOT be attributed to MDMA-induced damage 
to DA-containing terminals in the accumbens because in a similarly treated 
group of rats in our laboratory, tissue levels of DA in the nucleus accumbens 
2 weeks after the last MDMA injection were slightly but significantly 
increased rather than decreased (ref). Furthermore, basal extracellular 
levels of DA measured by dialysis in awake, behaving rats were unchanged in 
MDMA-pretreated compared to control animals (ref). " Thus, this paper also 
reports the exact opposite of what the NEJM letter claimed, and says that 
there is no evidence of MDMA having a neurotoxic affect on dopamine.  

The DEA has long tried to link MDMA and Parkinson's.  MDMA and MPTP became 
illegal at the same time and DEA publicity lumped MDMA and MPTP together to 
try to raise fear about MDMA and Parkinson's. Now this letter in the NEJM 
tries to make the same claim.  Score one for the DEA.

Rick

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