Why Be Awake? (Re: A Theory of Sleep)

et_al at my-deja.com et_al at my-deja.com
Fri Oct 12 01:04:51 EST 2001


On Fri, 12 Oct 2001 00:09:37 +1000, "John H." <John at faraway.com.au>
wrote:

>MDMA has been demonstrated to cause extensive damage to serotonin cells. One
>researcher has claimed that 100 uses of the drug is sufficient to cause
>damage 

A note of caution here, MDMA/Ecstasy can do damage even from the first
dose. See for example:

Colado MI, Granados R, O'Shea E, et al. (1999) 
"The acute effect in rats of 3,4-methylenedioxyethamphetamine (MDEA,
"eve") on body temperature and long term degeneration of 5-HT neurones
in brain: a comparison with MDMA ("ecstasy")."  
Pharmacol Toxicol, vol 84(6):261-6 

Certainly, psych disorders may be triggered by just one tablet.

>and increasing amounts of research point towards PERMANENTLY depleted
>serotonin resulting in mood and cognitive functions, will will probably only
>worsen with age. (Caveat: I have one study on rats that showed substantial
>serotonin recovery one year after loss from MDMA. There may be hope yet for
>
>all those who thought this was another safe drug but I doubt it.) 

AFAIK, the longest study is:

Hatzidimitriou G, McCann UD, Ricaurte GA. (1999) 
"Altered serotonin innervation patterns in the forebrain of monkeys
treated with (+/-)3,4-methylenedioxy- methamphetamine seven years
previously: factors influencing abnormal recovery."  
J Neurosci , vol 19(12):p 5096-10

which has shown that even after 7 years there is still significant
damage. 

>Not sure
>of the process that gives rise to this, can only speculate that as serotonin
>metabolism generates super anions, and this together with nitric oxide,
>released under some types of glutamate receptor activation(assuming high
>levels of glu in MDMA and LSD), can give rise to peroxynitrate , which
>nitrates tyrosine H and and generally does a lot of damage to cells.
>
Yes, there seem to be several factors at play, energy depletion within
the cell can interfere with it's ability to regulate ion balance, and
the ability to repair free radical/oxidation injury etc.  And its not
just 5-HT that gets hypersecreted, but dopamine too.
>
>After MDMA a person will feel 'washed out' for a few days, no matter how
>much they sleep. I suspect the serotonin is not waiting to be reabsorbed
>into vesicles, but has been lost forever, metabolised and gone. If it were
>just a matter of transport back to vesicles, then a day should be ample.

5-HT hypersecretion also seems to inhibit 5-HT synthesis from
L-Tryptophan.

>MDMA probably
>causes a low level but nonetheless deleterious inflammatory reaction. The
>subsequent release of cytokines like il1 and tnf will induce fatigue (hence
>why you feel tired when you get the flu and other viruses) and have been
>demonstrated to inhibit cerebral metabolism; not to mention causing cell
>death.

And there is now much work showing that cytokines may be involved in the
triggering of some psych disorderes, particularly anxiety and
depression.


Ian




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