'E' and MONOAMINES: What is the risk?

[David Longley]

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.
-- 
David Longley