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MAPS: Special Digest: MDMA and Health
-------------------
Mod Note: This morning I found 25 MAPS-Forum submissions in my inbox,
which must be a new record. The current MDMA discussion has been very
well-informed and provocative, so I decided to create this digest special
to accomodate all the excellent posts on this thread, while maintaining
the spirit of our five/day rule.
--Jon Frederick
-------------------
CONTENTS:
Strange info on MDMA tox, By Uzondu Jibuike
Re: Strange info on MDMA tox, By Dave Nichols
Risks and benefits, By Nancy A. Piotrowski, Ph.D.
Re: Strange info on MDMA tox, By Nicholas V. Cozzi, Ph.D.
Re: MDMA - health risks, By LarryLeeman/Rebecca Jervis
MDMA and society, By Simon Witter
Re: Strange info on MDMA tox, By Alex Gamma
MDMA and diabetics, By Ben J Williams Esq
Serious flaw in the MDMA & Memory study, By Per \"Zike!\" Carlbring
Re: People article correction (fwd), By Cyrus Mccandless
Re: People article correction! (fwd), By Stanley Fahn M.D.
------------------------------
From: Uzondu Jibuike <ucj@xxxxxxxxx>
Subject: MAPS: Strange info on MDMA tox
David,
See Neurotoxicology 1998, 19(3): 427-442, "An integrated hypothesis for
the serotonergic axonal loss induced by 3,4-methylenedioxymethamphetamine"
by Jon E. Sprague, Shannon L. Everman and David E. Nichols. They outline
the various theories re mechanisms for the axonal loss induced (at least
in animals) by high dose MDMA (MDA, MDE...).
Briefly (and perhaps poorly paraphrased, I'm sure I'll be reprimanded)
*their* hypothesis states that: MDMA induces acute release of both 5-HT
and DA; this is followed by depletion of intraneuronal 5-HT. Initially
released 5-HT activates post-synaptic 5-HT2A/2C receptors on GABA
interneurons resulting in decreased GABAergic transmission and increased
DA release and synthesis. DA is itself cytotoxic and the 5-HT uptake
carrier is known to transport DA as well. Excessive DA released may be
transported into the depleted 5-HT terminal where it is deaminated by
intraterminal MAO-B resulting in free-radical generation and the selective
degeneration of serotonergic axons and axon terminals.
ucj
You wrote:
The picture they are presenting here seems to be that the supposed 5-HT
toxicity of MDMA occurs when the MDMA somehow causes there to be too much
_dopamine_ in a _serotonergic_ synapse, which is then transported by the
_serotonin_ reuptake transporter in to, I assume, the presynaptic side,
where it is oxidized by MAO-B, releasing destructive hydrogen peroxide.
Does this make sense to anyone? I don't understand why MDMA would put
dopamine where serotonin should be; or why the serotonin transporter would
transport dopamine. Any explanation would be greatly appreciated.
David E. Nichols had the following comments re David's question:
---------- Forwarded message ----------
Date: Wed, 13 Jan 1999 16:56:52 -0500
From: Dave Nichols <drdave@xxxxxxxxxxxxxxxxxxx>
Subject: Re: MAPS: Strange info on MDMA tox
Dopamine increases to incredible levels, and extracellular DA is floating
around all over in the striatum. MDMA doesn't put it anywhere, it's just
like a dam that broke and spills dopamine all over the place. In fact, the
serotonin transporter *does* transport dopamine. Take away the serotonin
(which IS gone after MDMA) and the transporter will pull dopamine into the
serotonin neurons. There has been at least one, and I think maybe a second
study besides ours to show this.
I can tell you though that we have now done a definitive experiment and have
excluded the role of MAO-B in the neurotoxic process. It is still possible
that dopamine inside the 5-HT terminals is the toxic agent however.
dave
-------------------------
From: "Nancy A. Piotrowski, Ph.D." <npiotrowski@xxxxxxx>
Subject: risks and benefits
>From: Harry Sumnall <spun@xxxxxxxxxxxxxxx>
>To: MAPS FORUM <maps-forum@xxxxxxxx>
>
>As a footnote to the recent 'People' magazine discussion, I
>find it hardly surprising that such obvious errors are
>allowed into print when, what I assume to be the premiere
>'official' drugs information bureau, NIDA, includes in its
>MDMA web posting information that would certainly suggest
>links between MDMA and Parkinson's:
>
><http://www.nida.nih.gov/Infofax/ecstasy.html>www.nida.nih.gov/Infofax/ecs
tasy.html
Harry, I think you are mischaracterizing what is listed at the web address
noted above. The wording is very specifically worded in the brief presented
and carries detail far beyond what we might find in the popular press.
As a suggestion, perhaps you and interested others could work up a draft and
submit it as feedback to that site, as to how one could better describe the
potential risks and benefits of MDMA use, addressing the issues that are
already raised about methamphetamine and Parkinsonian symptoms. They have a
"feedback" option at the bottom of the page at that site--so why not send
something in as food for thought?
--------------------
From: "Nicholas V. Cozzi, Ph.D." <nvcozzi@xxxxxxxxxxxxxxxx>
Subject: Re: MAPS: Strange info on MDMA tox
At 01:58 AM 1/12/99 -0800, David wrote:
>"NMDA" (below) seems to be a typo. The picture they are presenting here
>seems to be that the supposed 5-HT toxicity of MDMA occurs when the MDMA
>somehow causes there to be too much _dopamine_ in a _serotonergic_
>synapse, which is then transported by the _serotonin_ reuptake transporter
>in to, I assume, the presynaptic side, where it is oxidized by MAO-B,
>releasing destructive hydrogen peroxide.
>
>Does this make sense to anyone? I don't understand why MDMA would put
>dopamine where serotonin should be; or why the serotonin transporter would
>transport dopamine. Any explanation would be greatly appreciated...
The serotonin transporter is actually quite promiscuous, it will transport many
amphetamine-like drugs. It doesn't have a particularly high affinity for
dopamine, though; the selectivity is about 20:1, i.e. it would take a 20-fold
higher concentration of dopamine to occupy the same number of transporters as a
given concentration of serotonin (see Hoffman BJ. Expression cloning of a
serotonin transporter: a new way to study antidepressant drugs.
Pharmacopsychiatry, 27, 16-22, [1994]). Still, dopamine *will* get in to the
serotonergic cell. The explanation for why dopamine would be put where
serotonin should be is simply that many synapses have multiple inputs, i.e. a
dopaminergic neuron and a serotonergic neuron may both synapse onto the same
postsynaptic cell. The MDMA-induced release of both neurotransmitters would
make them *both* accessible to each others' uptake transporter. Hope this
helps.
Nick
Nicholas V. Cozzi, Ph.D.
Department of Pharmacology
East Carolina University School of Medicine
Greenville, NC 27858
-----------------------------------
From: zuni@xxxxxxxx (LarryLeeman/Rebecca Jervis)
Subject: Re: MAPS: MDMA - health risks
>As far as I know, the only reason that diabetes has turned up as an exclusion
>criteria on MDMA protocols is excessive caution. I have heard personally from
>several diabetics who reported that MDMA was well tolerated. Has anyone ever
>actually heard of a diabetic having a problem related to their illness during
>an MDMA experience?
>
>Rick Doblin
>
Rick,
Diabetes would be a contraindication if it was present for long enough to
cause vascular disease such as coronary artery disease or cerebral vascular
disease. Rather than screen for these diseases diabetes may be used as a
surrogate due to increased incidence of stroke and myocardial infarction.
Larry Leeman MD
Larry Leeman MD, MPH
Family Medicine Obstetrical Fellow
University of Rochester Family Medicine
-------------------------------
From: "Simon Witter" <s-witter@xxxxxxxxxxxxx>
Subject: MDMA and society
Rick Doblin wrote:
<<There are anecdotal reports from several years ago of a decline in
violence and hooliganism associated with football (i.e. soccer) fans in
England after MDMA started replacing alcohol as the drug of choice by some
fans>>
Those reports may well be anecdotal, as in not conducted according to strict
scientific criteria, but by god are they true!
I started clubbing seriously in London in 1981, and was a very active
participant in the acid house summer of love in 1988, at which point all of
this happened.
MDMA had been seeping into England for a few years at the time, but first
became really widely available in the spring of 1988. The effect on football
fans was a side effect of the whole scene, but it was incredibly dramatic.
Clubs with the worst fans - like Manchester United, Chelsea and West Ham -
were transformed overnight. And I remember well going through
Rottweiler-guarded gates into a rave in an abandoned East End
factory where members of a notorious West Ham gang - who, weeks before, had
been cutting people up with razors - were dancing around in a state of
bliss, hugging other men.
If you weren't there, this may all be a bit hard to swallow, but consider
this... Football-related violence, which was epidemic in Britain 15 years
ago, is now a thing of the past. Sure, there's a hard core of career thugs
(and born xenophobes) who cause trouble at matches abroad in Europe, but the
atmosphere at most grounds in Britain is pure Disney.
I saw that transformation with my own eyes.
Simon Witter
PS: As for one of Holger's questions.... I have heard of people using LSD
that is three or four years old, though they have mainly kept it in ziplock
bags in their freezer compartments (for freshness). It still works fine,
apparently. Mind you, who knows what relationship, if any, street LSD in the
90s bears to the stuff Hofmann was talking about?
---------------------------------------
From: Alex Gamma <gamma@xxxxxxxxxxxx>
Subject: Re: MAPS: Strange info on MDMA tox
>"NMDA" (below) seems to be a typo. The picture they are presenting here
>seems to be that the supposed 5-HT toxicity of MDMA occurs when the MDMA
>somehow causes there to be too much _dopamine_ in a _serotonergic_
>synapse, which is then transported by the _serotonin_ reuptake transporter
>in to, I assume, the presynaptic side, where it is oxidized by MAO-B,
>releasing destructive hydrogen peroxide.
>
>Does this make sense to anyone? I don't understand why MDMA would put
>dopamine where serotonin should be; or why the serotonin transporter would
>transport dopamine. Any explanation would be greatly appreciated...
NDMA instead of MDMA is a typo. But the rest *does* make perfect sense. In
fact, it is, to my knowledge, the favored theory on *how* MDMA damages 5-HT
(serotonin) terminals. The idea is that, besides releasing serotonin, MDMA
also releases dopamine to a considerable extent. This excessive dopamine is
then transported - by the 5-HT presynaptic transporter - into serotonergic
nerve terminals, where its deamination by MAO-B creates oxidative insults
that destroy the terminal.
There are several lines of evidence supporting this seemingly complicated
theory. One of the most important findings is that when MDMA-induced
dopamine release is blocked, there will be no neurotoxic damage to 5-HT
terminals, *even though* serotonin release still occurrs. That led to the
conclusion that dopamine release is a prerequisite for MDMA neurotoxicity.
Alex
-----------------------------
From: "Ben J Williams Esq" <paxbjw@xxxxxxxxxxxxxxxxxxxxxxxxxxx>
Subject: MDMA and diabetics
Sympathomimetics are generally contraindicated in diabetics as
they can lead to a loss of diabetic control.
If this occurs in decongestants such as pseudoephedrine it is likely
to occur with the psychedelic amphetamines.
B
__________________________________________________
Ben J Williams MRPharmS
Medicinal Chemistry Group
School of Pharmaceutical Sciences
University of Nottingham
University Park
Nottingham
NG7 2RD
UK
Phone : +44 (0)115 9515151 x18304
Mobile: +44 (0)956 580807
Email : paxbjw@xxxxxxxxxxxxxxxxxxxxxxxxxxx
__________________________________________________
--------------------------
From: "Per \"Zike!\" Carlbring" <peca6657@xxxxxxxxxxxxx>
Subject: Serious flaw in the MDMA & Memory study
This posting is about the recent MDMA & Memory study
(http://www.erowid.org/mdma/mdma_study_memory/) published in "Neurology", Dec
1998.
As Alex Gamma said: "Don't believe anything unless you've checked it for
yourself!". So I did.
If you compare the MDMA group and the controll group in terms of "drug
history" (tabel 2), which is supposed to be held equal, there is a
significant difference between the two (Chi2[10]=39.06;p<0.01). As you can
see the MDMA group has a much higher use of ALL drugs! The whole study
suffers tremendously as the two groups are not matched in terms of drugs
other than MDMA. The present study CAN NOT say if the difference in memory
performace is due to MDMA use OR high use of other drugs (LSD, Cocaine,
Opiates, inhalants etc).
Also, the "drug history" only reports a dichotom ("Yes, I have used the
drug at least once" OR "No, never used") result. I dont think this gives
the full story. I would also like to know HOW OFTEN (& dosage!) one has
used the different drugs. To me it seems more likely that MDMA users has
used these other drugs more frequently than the controll group = Making
the differens between the groups EVEN bigger!
My interpretation is that there are more IMPORTANT variables that
separates the two groups than MDMA use, and therefore cannot be considered
valid!!
A question about the arbitrary strength of each pill: The authurs writes
that they asumed that 1 capsule equals 100mg MDMA. How did they come about
this amount? They never tell! Have they consulted the police (ie based on
the mean of the confiscated street-MDMA)? I dont know much about MDMA
pills, but are they allways 100mg each? Also, if one capsule equals 100mg,
how do they explain the spread (55mg-500mg)? I can understand "500mg" as
that would equal 5 capsules, but "55mg"? That is a little more than half a
pill... Strange...
Also, in their dependent variable (dose per month) they dont differenciate
between if you take 4 pills AT ONCE or 1 pill EACH WEEK. (I would think 4
pills at once would be more toxic?). Futhermore, they dont say anything
about long the monthly dosage has been consumed... (I would think 1 year
of 150 mg each month gives you less problems than 100 mg per month during
the last 17 years [see table 1]).
Could one interpret the study as "if you use MDMA, there is almost no harm
if you take moderate dosages (whatever that equals?), as their was no
associations on the 'cummulative life time use'".
Per Carlbring
Uppsala, Sweden
===================================================================
Snail-mail: Carlbring, Kungsg 54 B, S-753 21 Uppsala, Sweden.
Phone: +46-18-692003 - Email: Per.Carlbring.6657@xxxxxxxxxxxxx
ICQ Online: 15919069
In Medias Res: http://www.imr.c64.org
Personal homepage: http://www.imr.c64.org/zike/
===================================================================
From: Cyrus Mccandless <mccand+@xxxxxxxx>
Subject: Re: MAPS: People article correction (fwd)
Message-ID: <Pine.GSO.3.96L.990112160849.7338G-100000@xxxxxxxxxxxxxxxxxxx>
MIME-Version: 1.0
Content-Type: TEXT/PLAIN; charset=US-ASCII
I hope Dr. Fahn doesn't mind this being posted to the list.
Cyrus
Cyrus H. McCandless
Department of Neuroscience
University of Pittsburgh/CNBC
446 Crawford Hall
Pittsburgh, PA 15260
(412)624-4537
---------- Forwarded message ----------
Date: Tue, 12 Jan 1999 15:43:37 EDT
From: "Stanley Fahn M.D." <FAHN@xxxxxxxxxxxxxxxxxxxxxxx>
To: Cyrus Mccandless <mccand+@xxxxxxxx>
Subject: Re: MAPS: People article correction! (fwd)
I take note of your reprimand. I had been pondering the situation
and called People Magazine earlier today, before seeing this message
from you, and listed the errors. They told me they plan to print up
a correction........S. Fahn
> Date sent: Tue, 12 Jan 1999 10:53:59 -0500 (EST)
> From: Cyrus Mccandless <mccand+@xxxxxxxx>
> To: fahn@xxxxxxxxxxxxxxxxxxxxxxx
> Subject: Re: MAPS: People article correction! (fwd)
> Dear Dr. Fahn,
>
> In response to your reply to Mr. Doblin's query concerning People
> Magazine's misquote from your interview, I would have to reply that the
> duty of the scientist, indeed the reason why society finds him to be
> worth supporting, is to disseminate accurate reports of his findings to
> the general public. Unfortunately, Dr. Fahn, simply conceding that a lay
> publication has no interest in scientific accuracy is the easy road out.
>
> People magazine reaches a vastly greater segment of the population than,
> e.g. the Journal of Neuroscience. Therefore, it is perhaps even more
> important, and certainly of more relevance to the first bases of one's
> existence as a scientist, to correct, immediately, and in bold-face
> letters, so-to-speak, the People report, in which magazine many fewer
> people read the 'corrections' segments, than it would be in a reputable
> scientific journal, where such corrections would be noticed much more
> readily and may even be effectively disseminated through other channels.
>
> Dr. Fahn, as a role model for graduate students such as myself as well as
> for those in the general population lucky enough to have stumbled upon
> your work and that of others in their search for a career, inspiration, or
> even as a means of helping themselves to understand their medical,
> psychiatric, or drug-abuse problem, your dismissal of the People misquote
> as something that will just happen from time to time, is disheartening.
>
> By saying that the public is too ignorant to notice a correction or to
> make sense of it, you effectively discount the fact that you as an
> investigator, and myself as a student, work for them and by their consent
> only, and that as such, we owe them a debt of sincerity, accuracy, and
> good-faith effort, in exchange for which we gain our freedom of intellect,
> of pursuit, our dignity as contributing members of society, and our status
> as responsible citizens, educators, and even role models. Very few people
> outside of academia have been rewarded in this way, and we should value
> the mandate attached to these rewards as much as we value the rewards
> ourselves.
>
> I urge you to do what is necessary to see that the misquote is corrected,
> at least in print, not only for the sake of the group of scientists whose
> work is directly impacted by misinformation about the specific substances
> involved, but for the patients, the children and perhaps ailing family
> members of those who, however sadly, draw their news of the world from
> People; and for those of us who are students, either formally or
> informally, of any branch of the sciences, and who should be educated
> within the context of their ultimate duty and the quite reasonable cost of
> their academic freedoms.
>
> Thank you for your time.
> Best Wishes,
>
> Cyrus
>
> Cyrus H. McCandless
> Department of Neuroscience
> University of Pittsburgh/CNBC
> 446 Crawford Hall
> Pittsburgh, PA 15260
>
> (412)624-4537
>
>
>
------------------
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