From: lamontg@stein.u.washington.edu (Lamont Granquist)
Subject: Re: MDMA and self-esteem
Organization: 'Operation: Mindcrime'
Date: Tue, 15 Dec 1992 03:30:53 GMT

copley-devon@cs.yale.edu (Devon Copley) writes:
>Unfortunately (and believe me, I find it unfortunate), the above is not
>QUITE accurate...and MDMA is *definately not* a "damn safe drug." 

The only thing *definite* about MDMA is that there is a lot of
studies being badly interpreted. 

>Sure, it won't kill you.  That's the good news.  But the research that
>is available (and there's precious little of it, on humans or animals)
>implies the possibility of neural damage.  The animal study Lamont
>mentions found 5-HT degradation from even small doses, which was indeed
>reparable, but large doses caused degradation that was NOT reversed
>even a full year later.  Admittedly these doses were *very* large
>relative to the size of the rats they were testing.  The researchers
>pointed out, though, that the neurons that DID grow back may have been
>physical but not functional replacements -- in otherwords, they might
>not have grown back the same way.  [I'm sorry, I can't remember this
>reference, but if you really want it I can probably dredge it up.]

You're correct.  They were:
  o administered I.V.
  o administered over consecutive days with a total dosing that was *very* 
    large even in the studies which showed the least amount of
    neurotoxicity.
  o and the human:animal ratio was computed using body mass not brain
    mass which is likely the important factor.

ps. just run a medline search on Ricaurte for all the references to MDMA
    neurotoxicity research of that kind.

>MUCH more disturbing than the rat study, however, are the surveys of
>humans who have taken the drug.  Nearly all users report that the "good
>effects" of Ex get weaker each time they take it.

That happens with LSD also...  the first time you take it it blows your
mind, then its not as fun after you get used to it.  

  In fact, researchers
>were unable to find any "heavy users" of MDMA;

Send them over here, I'll introduce them to some heavy users.

 the usage curve drops
>off quickly, assumedly as the Ex high gets less and less satisfying.
>The implication here [drawn by the researchers, not me]?  Ecstasy
>*might* damage the very neurological subsystems responsible for its
>wonderful effect.

Well, if you're going to postulate morphological changes in the brain
functions...  how about 5-HT and DA receptor desensitization leading to
a decreased effect of MDMA and also benefitial antidepressant and anxiolytic
effect similar to pharmacotherapeutic reuptake inhibitors?  Not that I
conceide the point, but simply that its not necessarily harmful.

>Combine the two studies and you come up with the truly disturbing prospect
>of 5-HT degradation in humans.  Brain damage: subtle, not crippling, but 
>perhaps irreparable. 

Wrong you come up with nothing conclusive.  Hell, dogs don't even show signs
of neurotoxcity at all, who says that species-species differences aren't
enough so that humans don't have to worry about it at all?

>On the other side, though, a large majority of the human subjects reported
>that "the best day of their lives" was on Ecstasy.

Makes it sound like a simple euphoriant.  Read some of the other testimonies
as to how the drug can undo psychological damage...

>I won't give advice, but *I* am going to *STOP* at 2 or 3 doses.  The best
>day of my life is worth a little bit of 5-HT degradation.

You probably wont get any.  In an unpublished study by Ricaurte (which was
used in the FDA IND for MDMA recently approved) he found that p.o. 
administration of the "human equivalent" of 200mg of MDMA in Rhesus Monkeys
2 weeks apart for eight weeks produced no evidence at all of neurotoxic
damage.

And fenfluramine has been shown to be equally or more damaging than MDMA
in animal models, and that drug has been used by millions of people.  That
no neuropsychiatric side effects have been reported tends to suggest that
any that might exist are incredibly slight.  Compare persistant use of MDMA
and fenfluramine with persistant EtOH use - Which one causes more harm based
on this?  It seems rather clear to me, even in the worst case... 

>In any case, ECSTASY IS NOT A "DAMN SAFE DRUG" -- at least, it hasn't been 
>shown to be one yet, and the possibility exists that it is quite harmful.
>More research is needed before ANYONE (including me) can say for sure how 
>safe or unsafe it is.

I'm satisfied that its a damn safe drug.  All the human studies and all the
realistic animal models show no evidence of neurotoxicity.  And
pharmacologially and neurotoxicologically similar drugs used in humans don't
show persistant effects.

-- Lamont "I can spew more polysyllabic pharmacological terms than you can"
   Granquist

-- 
Lamont Granquist  lamontg@u.washington.edu
  "When dogma enters the brain, all intellectual activity ceases."
                                      -- Robert Anton Wilson