From: [lohr b t] at [astro.ocis.temple.edu] (Muse)
Newsgroups: alt.drugs
Subject: Re: Ecstacy causes brain damage
Date: 15 Nov 1994 04:39:10 GMT
Ollie Cornes ([o--l--e] at [smollow.demon.co.uk]) wrote:
: Discuss.
: Has any study ever been done that in any way proves/suggests this? Has
: anyone ever seen this for themselves? How do you define brain damage?
I wrote this out to post a while back, but then discussion seemed to die.
Anyway....
A lot of discussion seems to happen on the topic of MDMA neuron depletion.
Following are notes I took reading various articles in the Annals of the New
York Academy of the Sciences one week when I was bored. The Academy seems to
hold conferences on a single topic in which they invite everyone doing
research in the field. There are ten to twenty major presentations and then
a serious of small poster presentations. Important aspects of the question
and answer session are printed after each presentation. The research provides
a possible source of the MDMA rumour of serotonin and dopamine depletion as
well as the rumour that it causes Parkinson's disease.
The research, though not extensive, indicates that MDMA does cause long
term dopamine and serotonin neuron damage. A hypothesis on the cause of
Parkinson's seems to indicate that dopamine and serotonin neurons are being
constantly depleted and everyone would eventually get Parkinson's if they
lived long enough (around age 110). MDMA would then seem to reduce the age
at which one would acquire the disease. So instead of necessarily causing the
disease, it would make you get it sooner. However, large dosages of
anti-oxidants such as vitamins C and E appear to decrease the amount of
depletion caused by MDMA. I have cited a poster paper on the safety of
mega-doses of vitamin C. Finally, I threw in an interesting tidbit about
locations of vitamin C in the human brain. The eye appears to have an
unusually large amount of vitamin C, which provides some insight into the
practise of consuming large quantities of it when tripping to increase
visuals.
This is not fact, but my interpretation of what I've read. I have no degree
in any of this, but I remember enough high school and college biology to
get the general gist of what was being said. Someone more qualified might
want to review the conferences cited to affirm my accuracy.
- Muse
(There was some water damage in my notebook and some words got washed away.
These are represented by question marks.)
=============================================================================
An Essay from The Mesocorticolimbic Dopamine System from the Annals of the
New York Academy of Sciences, Volume 537, 1988.
=============================================================================
Neurotoxicity in Dopamine and 5-Hydroxytryptamine Terminal Fields: A Regional
Analysis in Nigrostriatal ????? Projections by SEIDEN, COMMINS, VO????
=============================================================================
Methamphetamine (MA) - d-N-methyl-Beta-phenylisopropylamine
- Enchances release of dopamine (DA), norepinephine (NE) and
5-hydroxytryptamine (5-HT) from synaptosomes.
PHYSIOLOGICAL/BEHAVIOURAL EFFECTS
---------------------------------
- Cardiovascular stimulation, bronchodilation, mydriasis
- Effects psychomotor stimulation and anorexia
- Hypodipsia, respiratory stimulation, hyperthermia
- Used as an appetite suppresant and to increase mental/physical alertness
ABUSE EFFECTS
-------------
- Acute complication is a psychosis that can include paranoid delusions,
disordered thought, inappropriate aggressive behaviour and hallucinations
- AMPH & MA block reuptake and promote release of monoaminergic transmitters
NEUROTOXICITY OF MA
-------------------
- Rhesus monkeys given 28-48 mg/kg/day for 90-180 days showed profound DA
depletion 3-6 months later. This was also shown in rats, mice and cats.
- Guinea pigs, which metabolize MA in the same way as humans also showed
MA-induced toxicity.
- Doses observed to induce neurotoxicity are 25 to 100 fold higher than
generally used to produce physiological/biological effects (10-50 mg/??).
- An abuser may use up to 1-2 grams over 1-2 days. This is comparable to
neurotoxic doses.
?????? EFFECTS
--------------
- ??? reuptakes sites for DA reduced 50% by MA.
- MA given to rats eight times over four days at 50 mg/kg/dose.
- AMPH has same effect.
* Methylenedioxyamphetamine (MDA) methylenedioxymethylamphetamine (MDMA),
and fenfluramine cause long-term reduction in 5-HT and the number of 5-HT
uptake sites.
- Degenerating neurons observed in layers III-IV of somatosensory cortex.
May be related to observation of chronic MA users having somatosensory
abnormalities resulting in lesions to skin from excessive
scratching/picking.
* Degenerating terminals seen in hippocampus and degenerating neuronal
perikarya in somatosensory cortex following MDA and MDMA, respectively.
- DA degeneration is localized. 5-HT does not seem to be.
PROPOSED MECHANISM
------------------
- MA converts DA to 6-hydroxydopamine (6-OHDA) and 5-HT to
5,6-dihydroxytryptamine (5,6-DHT), compounds known to be neurotoxic to DA
and 5-HT respectively.
- Observed alpha-methyl-p-tyrosine (AMT), a competitive inhibitor of
tyrosine hydroxylase, the rate-limiting enzyme for DA synthesis, can
block neurotoxic effects of MA. Resperpine potentiates the effects of MA.
- MA induced toxicity is dependent on cytoplasmic DA
An Essay from Vitamin E: Biochemistry and Health Implications from the Annals
of the New York Academy of Sciences, Volume 570, 1989.
=============================================================================
Endogenous Toxin Hypothesis of the Etiology of Parkinson's Disease and a
Pilot Trial of High-Dosage Anti-Oxidants in an Attempt to Slow the Progression
of the Illness by STANLEY FAHN
=============================================================================
Parkinsonism is a neurological syndrome manifested by a combination of 2 or
more of the following symptoms: tremor at rest, rigidity, bradykinesia and
lost of postural reflexes.
PD is a progressive neurological disorder of the CNS in which there is a loss
of monoamine neurons in the brain stem nuclei (predominantly the substantia
nigra and the locus ceruleus) associated with eosinophilic cytoplasmic
inclusion bodies (Lewy bodies) in these neurons.
Dopamine levels in nigrostriatal fibres lowered. Replacement of dopamine
deficiency by levodopa therapy is most effective for reversing symptoms.
However, does not prevent worsening of disease over time.
ENDOGENOUS TOXIN HYPOTHESIS
---------------------------
- Neurons in locus ceruleus (norepinephrine-containing) are continually lost
with age. At youth levels are approx. 19,000 going to approx. 10,000 in
a person's 80s.
- In substantia nigra (dopamine-containing) cells also decreased from 400,000
at birth to approx. 250,000 at age 60.
- Neurons in the cerebral cortex are not lost.
- When dopamine content/cell population reaches 20% of youth levels, symptoms
of parkinsonism appear.
- Dopamine synthesising enzymes decrease while catabolic enzyme monoamine
oxidase types A & B increase with age.
- Suggest increased formation of homovanillic acid and hydrogen peroxide with
age. ???? be converted to neurotoxins superoxide and ?????
- Normal dopamine degredation causing Parkinsons at age 110.
- Various methods suggested to cause increase in PD:
@ Increased rate of dopamine degredation.
@ Fewer nigra cells at birth.
@ Accident in life reducing the number of nigra cells suddenly, so
fewer nigra cells.
- Excessive accumulation of free radicals occurs in patients with PD.
Possibly due to overload on scavenging system, a genetic or environmental
defect in scavenging system or microenvironment of specific nigra cells
being effected does not allow proper functioning of scavenging system.
(The scavenging system removes free radicals).
HIGH DOSAGE ANTI-OXIDANTS
-------------------------
- Uncontrolled study, though results can be compared with Tanner who used
identical theraputic treatment except without antioxidants.
- 3200 unit/day Vitamin E, 3 g/day Vitamin C.
- Average of 2.5-3 year delay of onset of serious PD symptoms (when l-dopa
treatment becomes necessary to avoid threat to occupational, physical or
social disability) as compared to Tanner's patients from original
treatment of mild symptoms.
Essays from The Third Conference on Vitamin C from the Annals of the New York
Academy of Sciences, Volume 498, 1987.
==============================================================================
Ascorbic Acid Reduces and Diethyldithiocarbamate Potentiates MA-induced
Dopamine and Serotonin Depletions by GEORGE C. WAGNER & MICHAEL J. DEVITO
==============================================================================
- Recent studies have shown MA leads to the in vivo production of
6-hydroxydopamine and 5,6-dihydroxytryptamine, the respsective neurotoxins
of DA and 5-HT.
- Ascorbic Acid (AA) reduced, thought not eliminating, DA and 5-HT
terminal ending depletion as a result of MA.
- DDC potentiates such depletion.
==============================================================================
Effects of High-level Vitamin C Ingestion by JERRY M. RIVERS
==============================================================================
The practise of ingesting large quantities of ascorbic acid will not result
in calcium-oxalate stones, increased uric acid excretion, impaired vitamin
B-12 status, iron overload, systemic conditioning (i.e.: scurvy if taken off
high doses; addiction) or increased mutagenic activity in healthy individuals.
==============================================================================
Ascorbic Acid Distribution Patterns in Human Brain: A Comparison with Nonhuman
Mammalian Species by ARVIN F. OKE, LESLIE MAY and RALPH N. ADAMS
==============================================================================
- Hippocampus and hypothalamus consistently show high AA levels when
compared with other structures in the CNS.
- Concentration of AA is substantially high in ocular tissues.
--
Trevor Lohrbeer, Muse
URL: http://astro.ocis.temple.edu/~lohrbt/