LETTERS
Ecstasy
and
neurodegeneration
Advice
is
that
"less
is
more"
EDITOR,-A
Richard
Green
and
Guy
M
Good-
win
rightly
point
out
that
the
risk
of
long
term
consequences
of
neurodegeneration
associated
with
the
use
of
ecstasy
(3,4-methylene-
dioxymethamphetamine)
may
be
greater
than
the
risk
of
death
from
acute
toxicity.'
Having
reviewed
the
compelling
evidence
linking
ecstasy
with
neurotoxicity
in
animals,
they
omit
what
is
perhaps
the
strongest
indication
of
neurotoxicity
in
humans.
A
universal
finding
of
descriptive
studies
of
users
of
ecstasy
is
that
the
first
ecstasy
tablet
is
the
best
and
that
with
subsequent
use
the
desired
effects
decline
and
side
effects
increase.24
As
ecstasy
is
pharmacologically
active
for
only
a
few
hours
and
even
frequent
users
usually
limit
their
use
to
weekends,
neurotoxicity
seems
a
more
likely
explanation
than
tolerance
through
neu-
roadaptation.
Even
newsgroups
on
the
Internet
that
promote
the
use
of
ecstasy
are
now
debating
not
whether
it
causes
serotoninergic
nerve
cell
damage
but
whether
the
result
is
detrimental,
inconsequential,
or
even
beneficial,
with
general
advice
to
users
being
that
"less
is
more"
and
"more
than
one
tablet
once
a
month
is
an
overdose."
In
Britain,
use
of
ecstasy
is
inextricably
related
to
dance
culture
and
"raves."
Perceiving
a
dimin-
ished
effect
as
being
due
to
poor
quality,
ecstasy
"ravers"
often
"stack
up,"
taking
ecstasy
in
higher
doses
and
more
frequently
than
reported
elsewhere.
Whereas
only
a
fifth
of
the
Stanford
cohort2
and
a
third
of
the
Sydney
cohort3
had
We
receive
more
letters
than
we
can
publish:
we
can
currently
accept
only
about
one
third.
We
prefer
short
letters
that
relate
to
articles
published
within
the
past
four
weeks.
Letters
received
after
this
deadline
stand
less
chance
of
acceptance.
We
also
publish
some
"out
of
the
blue"
letters,
which
usually
relate
to
matters of
public
policy.
When
deciding
which
letters
to
publish
we
favour
originality,
assertions
supported
by
data
or
by
citation,
and
a
clear
prose
style.
Wit,
passion,
and
personal
experience
also
have
their
place.
Letters
should
have
fewer
than
400
words
(please
give
a
word
count)
and
no
more
than
five
references
(including
one
to
the
BMY
article
to
which
they
relate);
references
should
be
in
the
Vancouver
style.
We
welcome
pictures.
Letters
should
be
typed
and
signed
by
each
author,
and
each
author's
current
appointment
and
address
should
be
stated.
We
encourage
you
to
declare
any
conflict
of
interest.
Please
enclose
a
stamped
addressed
envelope
if
you
would
like
to
know
whether
your
letter
has
been
accepted
or
rejected.
Letters
will
be
edited
and
may
be
shortened.
taken
ecstasy
on
more
than
10
occasions,
over
half
of
a
sample
in
London
had
used
it
more
than
20
times.5
Media
campaigns
focusing
on
deaths
from
use
of
ecstasy
are
worse
than
useless:
they
no
more
deter
young
people
from
taking
ecstasy
than
reports
of
deaths
in
an
avalanche
stop
me
from
taking
skiing
holidays.
Exaggerated,
sensational-
ist
drug
prevention
campaigns
are
recognised
as
such
by
young
people
and
decrease
the
chance
of
prudent
advice
being
taken
seriously.
JOHN
MERRILL
Consultant
in
drug
dependence
Drugs
North
West,
Manchester
M25
7BL
1
Green
AR,
Goodwin
GM.
Ecstasy
and
neurodegeneration.
BMJ
1996;312:1493-4.
(15
June.)
2
Peroutka
SJ,
Newman
H,
Harris
H.
Subjective
effects
of
3,4-methylenedioxymethamphetamine
in
recreational
users.
Neuropsychopharmacology
1988;1:273-7.
3
Solowij
N,
Hall
W,
Lee
N.
Recreational
use
of
MDMA
in
Syd-
ney:
a
profile
of
ecstasy
users
and
their
experiences
with
the
drug.
BrjAddict
1992;87:1161-72.
4
Greer
J,
Tolbert
R.
Subjective
reports
of
the
effects
of
MDMA
in
a
clinical
setting.
J
Psychoactive
Drugs
1986;18:319-28.
5
Winstock
AR.
Chronic
paranoid
psychosis
after
misuse
of
MDMA.
BM_
1991;302:1150-1.
No
evidence
of
neurotoxicity
exists
EDrIOR,-In
their
editorial
on
ecstasy
(3,4-
methylenedioxymethamphetamine)
and
neuro-
degeneration
A
Richard
Green
and
Guy
M
Goodwin
state
that
young
people
who
misuse
ecstasy
should
be
fully
informed
of
the
risks,
which
they
claim
are
considerable
in
the
long
term.'
The
authors
cite
animal
studies
indicating
that
recreational
use
of
ecstasy
can
cause
neuro-
toxicity
to
the
serotoninergic
systems
of
the
brain.
The
fact
that
the
United
States
Food
and
Drug
Administration
recently
(in
May)
approved
dexfenfluramine
for
daily
long
term
use
could,
however,
imply
that
ecstasy
is
similarly
safe
for
long
term
use.
This
is
because
much
evidence
of
neurotoxicity,
based
on
markers
in
animal
studies,
applies
to
research
on
both
drugs.
In
this
context
G
A
Ricaurte
(whose
evidence
is
cited
in
the
editorial)
believes
that
neurotoxicity
pro-
duced
by
dexfenfluramine
is
identical
with
that
produced
by
ecstasy
(personal
communication,
October
1995).
Indeed,
Green
himself,
with
col-
leagues,
has
implicitly
equated
the
neurotoxic
effects
of
ecstasy
with
those
produced
by
fenfluramine.2
Recent
research
casts
further
doubt
on
the
methods
used
to
provide
evidence
of
neurotoxic-
ity
in
humans.
Postmortem
examination
of
long
term
users
of
methamphetamine
showed
reduced
levels
of
dopamine
nerve
terminal
markers
similar
to
those
seen
after
use
of
ecstasy
and
fenfluramine.
But
the
study
went
on
to
con-
clude
that
"levels
of
DOPA
decarboxylase
and
the
vesicular
monoamine
transporter,
known
to
be
reduced
in
Parkinson's
disease,
were
normal.
This
suggests
that
chronic
exposure
to
metham-
phetamine
does
not
cause
permanent
degenera-
tion
of
striatal
dopamine
nerve
terminals
at
the
doses
used
by
the
young
subjects
in
our
study."3
The
editorial
suggests
that
use
of
ecstasy
may
eventually
produce
effects
similar
to
Parkinson's
disease,
as
was
the
case
with
MPTP
(N-methyl-
4-phenyl-1,2,3,6-tetrahydropyridone).
This
is
unlikely
because
the
effects
of
MPTP
were
seen
immediately.
The
analogy
with
MPTP-used
by
those
who
lobby
for
the
prohibition
of
ecstasy
in
the
United
States-was
long
ago
shown
to
be
unfounded.4
The
strongest
evidence
against
such
damage
being
a
normal
consequence
of
inges-
tion
of
ecstasy
must
surely
be
the
small
number
of
casualties
among
the
large
number
of
users
over
the
past
two
decades.
Psychiatric
conse-
quences
are
generally
restricted
to
people
with
considerable
premorbid
psychopathology,
poly-
substance
misuse,
and
histories
of
taking
exces-
sive
amounts
of
ecstasy.'
There
is
no
evidence
to
show
that
ecstasy
is
neurotoxic
in
humans.
Since
the
possibility
of
neurotoxicity
is
a
matter
of
great
public
concern,
however,
it
should
be
urgently
investigated
by
research
on
human
volunteers.
NICHOLAS
SAUNDERS
Independent
researcher
14
Neal's
Yard,
London
WC2H
9DP
http://ecstasy.org/
1
Green
AR,
Goodwin
GM.
Ecstasy
and
neurodegeneration.
BMJ
1996;312:1493-4.
(15
June.)
2
Colado
MI,
Murray
TK,
Green
AR.
5-HT
loss
in
rat
brain
fol-
lowing
3,
4-methylenedioicymethamphetamine
(MDMA),
p-choroamphetamine
and
fenfluramine
administration
and
effects
of
chlormethiazole
and
dizocilpine.
Br
J
Pharmacol
1993;108:583-9.
3
Wilson
JM,
Kalasinsky
KS,
[every
AI,
Bergeron
C,
Reibel
G,
Anthony
RM,
et
aL
Striatal
dopamine
nerve
terminal
mark-
ers
in
human,
chronic
methamphetamine
users.
Nature
Medicine
1996;2:699-703.
4
Beck
J,
Morgan
P.
Designer
drug
confusion:
a
focus
on
MDMA.J
DrugEduc
1986;16:
267-82.
5
McGuire
PK,
Cope
H,
Fahy
TA.
Diversity
of
psychopathology
associated
with
use
of
3,4-methylenedioxymeth-
amphetamine
("Ecstasy").
BrJ
Psychiatry
1994;165:391-5.
Tablets
often
contain
substances
in
addition
to,
or
instead
of,
ecstasy...
ED1TOR,-A
Richard
Green
and
Guy
M
Good-
win
emphasise
the
potential
long
term
neurotox-
icity
associated
with
the
use
of
ecstasy
(3,4-methylenedioxymethamphetamine).'
Small
studies
of
clinical
populations
have
already
given
a
clue
to
the
possible
functional
impact
of
this
drug
on
the
human
nervous
system
by
showing
a
wide
range
of
psychopathology
associated
with
its
short
term
ingestion.2
3
They
also
point
out
that
people
who
metabolise
the
drug
quickly,
although
perhaps
protected
from
acute
toxicity
(some
of
which
will
no
doubt
be
idiosyncratic
in
nature),
may
be
more
at
risk
of
longer
term
neu-
rodegeneration
than
other
people.
Those
who
metabolise
the
drug
quickly
may
possibly
also
experience
"desirable"
effects
of
the
drug
for
a
shorter
time
than
other
people.
This
might
lead
them
to
take
increasing
doses
to
sus-
tain
the
wanted
effect,
with
this
compounding
any
potential
risk.
In
a
study
at
the
Maudsley
Hospital
many
subjects
have
reported
taking
over
10
tablets
in
an
evening;
some
have
reported
lifetime
use
exceeding
1000
tablets.
With
toxicity
in
animal
studies
being
associated
with
a
single
dose,4
such
lifetime
consumption
makes
the
like-
lihood
of
latent
functional
psychological
prob-
lems
even
more
likely.
Data
from
the
forensic
analysis
of
drugs
seized
by
the
police
and
customs
show
that
tablets
that
are
claimed
to
be
ecstasy
tablets
may
contain
a
variety
of
related
substances.
Tablets
are
commonly
found
to
contain
MDEA
(3,4-
methylenedioxyethylamphetamine),
MDA
(3,4-
methylenedioxyamphetamine),
or
MBDB
BMJ
VOLUME
313
17
AUGUST
1996
423
