MAPS: Dopamine transporter density in concomittant amphetamine andEcstasy users

[Harry Sumnall <spun@xxxxxxxxxxxxxxx>]

The Dutch research team of Reneman and colleagues have just published an
intriguing study investigating the effects of combined recreational use of
amphetamine + Ecstasy upon striatal dopamine (DA) transporter density in
dance drug users (Psychopharmacology (2002) 159:335-340; I have .pdf for
anyone who is interested in reading this). Reneman suggests 25% of Dutch
users regularly combine Ecstasy and amphetamine, my own figures suggest
that this is probably higher (at least in the UK). I've reproduced the
abstract below. NB "amphetamine" in this study most likely refers to
d-amphetamine and not methamphetamine, the latter of which is rarely used
in Western Europe.

As you will already know, MDMA is not thought to have neurotoxic effects
upon the brain's dopaminergic system in either rats or humans (although
mice show DA n.toxicity & some rats show an increase in markers of DA
function a couple of weeks after drug admin.). Briefly, Reneman and
colleagues argue that combined use of Ecstasy and amphetamine leads to a
decrease (approx 12%) in striatal DA transporter binding ratio that is not
seen in "sole" Ecstasy users. However, statistically significant decrements
were not seen when compared to "drug naive" control subjects. Furthermore,
sole Ecstasy users (abstaining for around 3 months) showed an increase in
DA transporter ratio which complicated this analysis [Reneman discusses
possible reasons for this observation]. I would have liked to seen an
amphetamine-control group to compare the E/d-amph data to but this was not
included. As this data stands we do not know whether the drop in DA
transporter binding was due the effects of the drug combination or
amphetamine alone. Reneman is of the opinion that it was the use of
amphetamine and not ecstasy which caused these changes.

Reneman also offers a rebuttal to Mintzer et al (1999), who you may
remember attributed Parkinsonian signs in a patient to amphetamine
substitution in Ecstasy tablets. If this were the case, Reneman argues,
sole Ecstasy users would also show a drop DA transporter binding density.
That this was not evident suggests that Mintzer et al were wrong to link
Ecstasy and Parkinsonism (as the letters to the editors of the New England
Journal of Medicine argued at the time).

I would have also liked to have seen a description of the effects of the
Ecstasy/d-amphetamine combination upon 5HT transporter binding. Unpublished
data in the rat suggests that this combination has neurotoxic effects over
and above the effects of MDMA alone. Hopefully this data will soon be
forthcoming.

Harry Sumnall
Dept Psychology
University of Liverpool
Liverpool
UK



"Use of amphetamine by recreational users of ecstasy (MDMA) is associated
with reduced striatal dopamine transporter densities: a [123I]-CIT SPECT
study - preliminary report
Liesbeth Reneman, , Jan Booij, Jules Lavalaye1, Kora de Bruin, Johannes B.
Reitsma, W. Boudewijn Gunning, Gerard J. den Heeten and Wim van den Brink


Abstract. Rationale: Tablets sold as ecstasy often contain not only
3,4-methylenedioxymethamphetamine (MDMA) but other compounds well known to
cause dopaminergic neurotoxicity, such as (meth)amphetamine. Furthermore,
the use of ecstasy in the Netherlands is often combined with the use of
amphetamine. However, little is known about the effects of ecstasy use or
the combination of ecstasy and amphetamine use on dopamine (DA) neurones in
the human brain. Objectives: This study was designed to investigate the
effects of ecstasy as well as the combined use of ecstasy and amphetamine
on the density of nigrostriatal DA neurones. Methods: [123I]-CIT SPECT was
used to quantify striatal DA transporters. Striatal [123I]-CIT binding
ratios of control subjects (n=15) were compared with binding ratios of
ecstasy users (n=29) and individuals with a history of combined ecstasy and
amphetamine use (n=9) after adjustment for age. Results: Striatal
[123I]-CIT binding ratios were significantly lower in combined ecstasy and
amphetamine users compared to sole ecstasy users (6.75 versus 8.46,
respectively: -20.2%, P=0.007). Binding ratios were significantly higher in
ecstasy users when compared to controls (8.46 versus 7.47, respectively:
+13.2%, P=0.045). Conclusions: These initial observations suggest that the
sole use of ecstasy is not related to dopaminergic neurotoxicity in humans.
In contrast, the reported use of amphetamine by regular users of ecstasy
seems to be associated with a reduction in nigrostriatal DA neurones.

Keywords. Ecstasy - Amphetamine - Neurotoxicity - DA transporter -
[123I]-CIT SPECT"



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