MAPS: How strong is the evidence that brain serotonin neurons are damagedin human users of ecstasy?

[Harry Sumnall <spun@xxxxxxxxxxxxxxx>]

Dear Forum,

A quite balanced (and timely) review has appeared in the journal
Pharmacology Biochemistry and Behaviour (v71:4) that will be of interest to
all MDMA scholars, no matter which side of the fence you sit on with
regards to the neurotoxicity issue. You may remember that Dr Kish, the
author, published a very well publicised study a couple of years ago which
described the apparent depletion of striatal 5HT in a recently deceased
polydrug user. Dr Kish, describes how he believes that those earlier
findings may have been the result of the (reversible) effects of acute MDMA
ingestion.

"How strong is the evidence that brain serotonin neurons are damaged in
human users of ecstasy?,

[I have a .pdf for anyone who would like to receive it]

Pages 845-855

Stephen J. Kish




Abstract:

Understanding the diverse functions of serotonin in the human brain can be
obtained through examination of subjects having a lower than normal number
of brain serotonin neurons. Behavioral abnormalities consistent with brain
serotonergic damage have been reported in some polydrug users who also use
the neurotoxin ecstasy (methylenedioxymethamphetamine, MDMA). This review
evaluates the evidence from neuroimaging studies that brain serotonergic
damage is a feature of human users of ecstasy. To date, neuroimaging
studies designed to establish whether levels of brain serotonin neurons are
lower than normal in ecstasy users have employed radioligands that bind to
one component of the serotonin neuron, the serotonin transporter (SERT).
Because these studies are methodologically flawed in terms of reliability
or validity of the SERT measurement and appear to have employed polydrug
users, no definitive information is yet available on the question of
ecstasy toxicity to human brain serotonin neurons. Until these issues are
resolved, it cannot be assumed that ecstasy exposure represents a chronic
serotonin deficiency condition.

...
Conclusions

1. It is likely, on the basis of animal data, that ecstasy, at some dose,
will damage serotonin neurons in human brain. However, because of
methodological problems in the limited number of studies conducted in the
human, no conclusions can yet be established on ecstasy toxicity in human
brain or whether ecstasy exposure represents a chronic serotonin deficiency
syndrome.

2. The theoretical limitation of studies relying on neurochemical markers
of the integrity of serotonin neurons, which can be up- and down-regulated
independently of neuronal number, to assess serotonin neuronal damage
should be recognized."



Harry


__________________________________
Dr Harry Sumnall
Psychopharmacology Research Group
Department of Psychology
Eleanor Rathbone Building
Bedford Street South
University of Liverpool
Liverpool
L69 7ZA
UK

+44 0151 794 2177
spun@xxxxxxxxx
www.liv.ac.uk/Psychology

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