'E' and MONOAMINES: What is the risk?
David at longley.demon.co.uk
Wed Apr 12 08:47:50 EST 1995
ECSTASY AND THE ROLE OF MONOAMINES
Some months back we had a BBC HORIZON programme here where some
researcher claimed that MDMA was a 5HT neurotoxin, something like
6-OHDA is for the catecholamines. In the early 1980s I was using
indoleamine (5HT) and catecholamine (NA and DA) neurotoxins to
examine the role of these systems in reward and punishment.
(National Institute for medical Research, London). The 5HT toxin
was 5-7 DHT I recall.
Anyway, the researcher on the HORIZON programme said MDMA
depleted cortical 5-HT, and did so permanently!. I thought this
pretty severe given that so many young folk are taking so much of
this stuff AND that in the same programme some other researcher
was doing human experiments with MDMA!!.
I did a PSYCHLIT (Psychological Abstracts 1974-1994) search at
the time, and pulled off about 10 articles on MDMA and
neurotoxicity. Conclusion... half said it was, half said it
wasn't. This seems very odd. My recollection is that when you do
in vivo lesions with these neurotoxins, you check the efficacy
via HPLC (High Pressure Liquid chromotographic) analysis of the
concentrations of specific monoamines in different areas of the
brain known to be invervated by cell bodies in the brain stem
(and thus get a pretty good idea as to how well you have knocked
the ascending systems out). In rats, I thought there was no
recovery of function, and with 5-7DHT and 6-OHDA (which do not
pass the blood brain barrier incidentally) the effect is not just
a reserpine like induced depletion of transmitter. No doubt a
critical factor in all of this is dose level. The amount taken as
oral 'E' is no doubt very low compared to the pharmacological
does delivered intracranially, or even the does of DSP-4 (N-2-
chloroethyl-N-ethyl-2-bromo-benzene hydrochloride) used to zap
central Noradrenaline by IP injection. (Incidentally, if anyone
can bring me up to date on research using DSP-4 and the
behavioural consequences, please e-mail me).
It's all very complicated, and one assumes that MDMA like ampheta
mine does cross the blood-brain barrier. I would have thought
that if there WAS any sound evidence to suggest that MDMA caused
ANY permanent damage to the monoamines then there would have been
a LOT of academic and PUBLIC coverage. However, the high redundan
cy of the monoamine systems worries me. Some years ago there was
a report (another TV Horizon programme) on another designer drug
(PCP) and a synthesis problem. A number of users came down with
premature Parkinsonism (more like those described in 'Awakenings'.
Is it a viable hypothesis that the price for long term recreation
al use of MDMA and other designer drugs may be basal ganglia dis-
orders earlier in life? Could it be that users are only protected
now because of a high degree of redundancy in the monoamine paths?
I recall a paper by Hornekewitz (sp?) in the early 1980s on the
density of of forebrain NA declining with age (in rats).
I'd be interested to hear some professional views on these issues.
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