PRACTICE

IN BRIEF

1
2
3
4

MDMA or Ecstasy is widely used and popularly regarded as safe

Systemic effects may include sudden death.
Excessive thirst is quenched by the consumption of sugary carbonated drinks.
Tooth surface loss and TMJ symptoms may result from tooth clenching and grinding

Ecstasy related periodontitis and

mucosal ulceration a case report
1

W. J. Brazier, D. K. Dhariwal, D. W. Patton, and K. Bishop,

Methylenedioxymethamphetamine (MDMA) more commonly known as Ecstasy is a widely used recreational

drug. The oral and systemic effects associated with its use have been well documented. This paper
highlights a previously unreported complication of MDMA use on the oral mucosa. MDMA periodontitis is
illustrated with a case report and the local oral and systemic effects of MDMA use outlined.
impu-rities

in

the

3,4

MDMA and other

less addictive drugs
Methylenedioxymethamphetamine (MDMA) is a 3,4-methylenedioxysuch as Cannabis
ring sub-stituted amphetamine which is more com-monly known byhas been considered.

tablets.
Metabolism occurs

by
demethylation
primarily in the liver
and brain, catalysed
by
cytochrome
5
p450, although up to
75% of the drug is
eliminat-ed
unchanged
via
2
urinary excretion.

1
systemic
several names such as XTC, E and Love Drug. MDMA was first The
effects
associated
synthesized in 1914 for use in chemical warfare, however it was not
used therapeu-tically until the early 1970s when psychol-ogists used it with the use of
MDMA have been
2
as a facilitating agent for psy-chotherapy. It is now a class A listedwell documented and
drug
are summarised in
Table 1. Acute toxicity effects are not
dose related nor in
the majority of cases
are they caused by

under the 1971 Misuse of Drugs Act. TheCorrespondence

and requests for
illegal use of MDMA has become wide- offprints to: Miss
K Dhariwal,
spread in Britain, popularised in the earlyDMaxillofacial
1990s at raves. It is a sympathomimetic Unit, Morriston
stimulant which is taken orally, or occa- Hospital,
Swansea SA6
sionally injected intravenously, and causes a 6NL, Wales
sense of euphoria, insomnia and sup-pressesE-mail:
appetite. It is relatively easy to obtain and daljitdhariwal@
hotmail.com
fashionably regarded as a safe drug despite
serious medical sequelae including death.
Decriminalisation of
Refereed
Paper
Received
13.05.02;
1
Accepted
Senior House Officer in Oral and Maxillofacial Surgery,
24.10.02
2
Specialist Registrar in Oral and Maxillofacial Surgery,
British
3
4
Consultant in Oral and Maxillofacial Surgery, Consultant Dental
in Restorative Dentistry and Implantology, Maxillofacial Unit,
Journal 2003;
Morriston Hospital, Swansea, SA6 6NL,Wales

194: 197199

Table 1
Systemic
effects
associated
with the use
of MDMA
Psychiatric
Agitation,
delirium,
panic
disorder,
flashbacks,
paranoia,
hallucination,
depression,
psychosis
and suicidal
ideation.

Oral implications
The interactions of
Ecstasy
with
mono-amine
oxidase inhibitors
and tricyclic antit
a
x
i
a
,

s
e
i
z
u
r
e
s
Neurological
,
A

t
r
e
m
o
r
,
t
i
c
s
,
n

ystagmus and
cerebral
haemorrhage
Cardio-vascular

e
m
a

Tachyarrythmias, hypertension,
myocardial ischaemia / infarction,
and ventricular ectopy Respiratory

H
e
p
a
t
o
r
e
n
a
l

P
u
l
m
o
n
a
r
y
h
y
p
e
r
t
e
n
s
i
o
n
a
n
d
o
e
d

Renal
failure,
urinary
retention,
myoglobinur
ia, jaundice,
hepatitis
and hepatic
failure
necessitatin
g liver
transplantati
15
on
Metabolic
M
e
t
a
b
o
l
i
c
a
c
BRITISH

i
d
o
s
i
s
,

r
h
a
b
d
o
m
y
o
l
y
s
i
s
,

h
y
p
o
n
a
t
r
a
e
m
i
a
,

h
y
p
e
r
t
h
e
r
m
i
a

h
y
p
o
g
l
y
c
a
e
m
i
a
,
DENTAL

G
a
s
t
r
o
i
n
t
JOURNAL

e
s
t
i
n
a
l
N
a
u
s
e
a
,
v
o
m
i
t
i
n
g
,
a
n
o
r
e
x
i
a
,
d
i
VOLUME 194 NO. 4

a
r
r
h
o
e
a
,
i
s
c
h
a
e
m
i
c
c
o
l
i
t
i
s
O
t
h
e
r
Disseminated intravascular
coagulation (DIC),
vasculitis, sexual
dysfunction, seretonin
syndrome, aplastic
anaemia and death.
FEBRUARY 22 2003 197

PRACTICE
se
mb
le
a
d tyr
e am
p ine
r rea
e cti
s on.
s Sel
a ect
n ive
ts ser
, oto
wnin
h reu
icpta
h ke
minh
a ibit
y or
b (S
e SR
p I)
r ant
e ide
s pre
c ssa
ri nts
b are
e co
d mp
i etit
n ive
t inh
h ibit
e ors
mof
aM
nD
aM
gA
e he
mpat
e ic
n me
t tab
o oli
f sm
T at
Mthe
J de
p bri
aiso
n qui
a ne
n hy
d dro
atxyl
y ase
p (C
icYP
al2D
f 6)
a en
cizy
alme
p sta

aige
n an
, d
r ma
ey

cio
us
se
dat
ion
an
d
ma
y
req
uir
e
gre
ate
r
qu
ant
itie
s
of
an
aes
the
tic
ag
ent
to
ac
hie
ve
pai
n
fre
e
D de
nta
r
u l
g tre
at
a
b me
u nt.
1
s
e
T
rs he
s
ora
h
o l
w eff
ect
a
s
t
o of
le M
r
D
a
M
n A
c
are
e
a
t
o ma
nif
l
o estati
c
al on
a
of
n the
a
sys
e
te
st mi
h
et c
ic eff
ect
s
s
a
n of
d the
c
dru
o g.
n Do
s
p
o
te
n
ti
at
e
t
h
e
a
c
u
te
a
d
v
e
rs
e
ef
f
e
ct
s
o
f
E
c
st
a
s
y.

c hin
ug
mare
e co
nm
temo
dn
o ac
r ute
aleff
mect
as
n of
if M
eD
st M
atA
i use
o.
n Th
se
o thi
f rst
Mma
Dy
Mbe
Aqu
u en
s ch
e ed
a by
r the
e co
s ns
u um
mpti
mon
a of
ri su
s gar
ey
d car
i bo
n nat
T ed
a dri
b nk
les
2 lea
. din
Dg
r to
y ext
mens
o ive
u cer
t h vic
, al
b car
r ies
u an
xd
is ero
msio
an.
n Th
d irst
jama
wy
clals
eo
n be
c qu

e
n
c
h
e
d
b
y
e
x
c
e
s
si
v
e
c
o
n
s
u
m
p
ti
o
n
o
f
w
at
e
r
a
n
d
s
el
fi
n
d
u
c
e
d
w
at
e
r
i
n
t
o
x
ic
at
i
o
n
is
r
e
c
o
g
n
is
e
d
i
n
p
at
ie

nts
wit
h
ecs
tas
y
poi
so
nin
g.
Th
e
Ec
sta
sy
ind
uc
ed
tri
p
ma
y
las
t
up
to
36
ho
urs
suc
h
tha
t
too
th
cle
nc
hin
g
an
d
gri
ndi
ng
is
pro
lon
ge
d.
Th
e
bru
xis
m
an
d
cle
nc
hin
g
ma
y
lea
d
to
mu
scl
e
ten
der
nes
s

a TS
n L)
d is
st co
if mp
f ou
n nd
e ed.
s 68
s
a
n
d Ta
c bl
o e
u 2
O
p ra
le l
d m
wa
it ni
h fe
st
t at
h io
e n
e s
x of
M
c D
e M
s A
si u
v se
e
c1 B
o ru
n xi
s
s m
u
2 T
m
p o
ti ot
h
o cl
n e
o n
f c
a hi
n
ci g
d
3 T
ic
b M
e J
ar
v th
e ro
r m
a y
g al
e gi
a
s,
t4 D
o e
o nt
al
t at
h tri
s ti
u o
rf n
a5 X
c er
e o
l st
o o
s m
ia
s
(6 M

u
c
o
s
a
l
u
l
c
e
r
a
t
i
o
n

y
not
de
scr
ibe
d
pre
viou
sly
,
oc
cur
rin
g
7 P as
e the
r
res
i
o ult
d of
o top
n ica
t
l
i
ap
t
pli
i
s cat
ion
of
the
T dr
h ug.
is
p C
A
a
p S
E
e
R
r
d E
P
e
O
s
R
c
ri T
b A
e
15
s
a
ye
c
aro old
m bo
p y
li wa
c
s
at ref
i
err
o ed
n to
o the
f
Or
M al
D an
M d
A M
u axi
s
llo
e
fac
a
ial
p Su
p rge
a
ry
r
Un
e
it
n by
tl his

g nf
e ul
n up
- per
e ant
r eri
a or
l lip
msw
e elli
d ng.
i Th
c ere
a ha
l d
p be
r en
a no
c his
ti tor
ti y
o of
n tra
e um
r a.
wTh
it e
h pat
a ien
ot
n ha
ed
d co
a mp
y let
h ed
is 14
t mo
o nth
rs
y of
o fix
f ed
g ap
e pli
ne an
r ce
a ort
l ho
mdo
a nti
l c
a tre
is at
e me
a nt
n4
d mo
p nth
ys
r pre
ex vio
i usl
a y,
a an
nd
d ha
ad a
p we
a ll
i ma

i
n
ta
i
n
e
d
d
e
n
ti
ti
o
n
w
it
h
g
o
o
d
o
r
al
h
y
g
ie
n
e.
T
h
e
r
e
w
e
r
e
n
o
p
at
h
o
l
o
g
ic
al
p
e
ri
o
d
o
n
ta
l
p
o
c
k
et
s,
ie
p
o
c
k
et
d

ept
hs
of
2
3
m
m
we
re
not
ed.
C
lini
cal
ex
am
ina
tio
n
rev
eal
ed
a
sw
elli
ng
of
the
ma
xill
ary
lab
ial
ves
tib
ule
in

h
U
L
1
(
2
1
)
a
t
Ft
i h
ge
.
s
1 i
t
Ce
l
i
n
i
c
a
l
p
h
o
t
o
g
r
a
p
h

o
f
M
D
M
A
t
o
p
i
c
a
l

a
p
op
f l
i
mc
ua
c t
oi
s o
a n
l
f
e
n
e
s
t
r
a
t
i
o
n

rel
ati
on
to
the
up
per
ce
ntr
al
d inc
e iso
f rs.
e Bo
c th
t
ma
a xil
s lar
s y
o ce
c
ntr
i
a al
t inc
e iso
d rs
ex
w
hib
i
t ite

d
G
r
a
d
e
II
m
o
b
il
it
y
a
n
d
w
e
r
e
te
n
d
e
r
t
o
p
e
r
c
u
s
si
o
n
,
b
u
t
w
e
r
e
o
t
h
e
r
w
is
e
s
o
u
n
d
.
I
n
ci
si
o
n
a
n
d
d
r
ai
n
a
g

e
of
the
pre
su
me
d
ac
ute
de
nto
alv
eola
r
ab
sce
ss
wa
s
per
for
me
d
an
d
yie
lde
d
ser
ou
s
flu
id
wh
ich
wa
s
se
nt
for
cul
tur
e.
Ro
uti
ne
blo
od
tes
ts
we
re
per
for
me
d.
Or
al
ant
ibi
oti
cs,
Pe
nic
illi
n
V
an
d
M
etr
oni

d an
a ge
z 5
o 10
x
l 10
e9
w /l
],
e pre
r do
e mi
c na
o ntl
my
meo
sin
e op
n hil
c s.
e Th
de
. ery
thr
a oc
b yte
o se
r di
a me
t nta
o tio
rn
y rat
st e
u (E
d SR
i )
e wa
ss
r ele
e vat
v ed
e at
a 23
l m
e m/
d hr
a [n
wor
h ma
it l
e ran
c ge
e 2
ll 10
cm
o m/
u hr]
n an
t d
( he
Wpat
C ic
C en
) zy
o me
fs
8 as
. par
2x tat
1e
0 tra
9 ns
/am
l ina
[ se
n (A
o ST
r)
man
ad
l ga
rm

m
a
g
l
u
ta
m
y
l
tr
a
n
sf
e
r
a
s
e
(
G
G
T
)
el
e
v
at
e
d
at
5
9
U
/l
a
n
d
4
3
U
/l
r
e
s
p
e
ct
i
v
el
y
[
n
o
r
m
al
r
a
n
g
e
A
S
T
=
0

4
0
U
/l
;
G
G
T
=
0

8
5
U

/l].
Mi
cro
bio
log
ical
cul
tur
e
yie
lde
d
vir
ida
ns
str
ept
oc
oc
ci,
sta
ph
ylo
co
cc
us
epi
der
mi
dis
an
d
cor
yn
eba
cte
riu
m
sp
eci
es,
co
nsi
ste
nt
wit
h
co
mme
ns
al
ora
l
flo
ra.
O
n
rev
ie
w
2
da
ys
lat
er
the
sw
elli
ng
ha
d
red
uc
ed
in
siz
e

a he
n un
d der
s lyi
y ng
st alv
e eol
mar
icbo
s ne
y an
md
p roo
t ts
o of
mthe
s UL
s1
u (21
b)
si an
dd
e UL
d2
. (22
M)
u wa
cs
o not
s ed
alwit
f h
e Gr
n ad
e e II
st mo
r bili
atty
i of
oU
n R2
o (12
f ),
t U
h R1
e (11
at),
taUL
c1
h (21
e)
d an
gd
i UL
n2
g (22
i )
v (Fi
a g.
w1).
it Th
he
e tee
x th
p we
o re
s all
u vit
r al
e on
o ele
f ctri
t c

a
n
d
t
h
e
r
m
al
p
u
l
p
te
st
i
n
g.
R
a
d
i
o
g
r
a
p
h
ic
e
x
a
m
i
n
at
i
o
n
c
o
n
fi
r
m
e
d
n
o
si
g
n
if
ic
a
n
t
l
o
s
s
o
f
b
o
n
y
s
u
p
p
o
rt

(Fi
g.
2).

D
eta
ile
d
qu
est
ion
ing
in
the
pre
se
nc
e
of
his
par
ent
s
rev
eal
ed
no
ad
dit
ion
al
inf
or
ma
tio
n.
Th
e
pat
ien
t
de
nie
d
usi
ng
an
y
top
ica
l
ag
ent
s
in
the
are
a.
H
e
wa
s
ref
err
ed
to
the
de
nta
l
hy
gie
nis

t E
f cst
o as
r y
o as
ra
a rec
l rea
h tio
y nal
g dr
i ug
e on
ne
e da
i y
n pri
st or
r to
u on
c set
ti of
o sy
n mp
, to
s ms
c an
ad
li sto
n red
g the
a dr
n ug
d in
p the
o up
li per
s ant
h eri
i or
n lab
g ial
. ve
Asti
t bul
t e
h adj
is ac
v ent
is to
it the
h sit
ee
r of
e per
p iod
o ont
rt al
e de
d str
t uct
h ion
a.
t Th
he
e pat
h ien
at
d de
u nie
sd
e us
de

o
f
o
t
h
e
r
r
e
c
r
e
at
i
o
n
al
d
r
u
g
s
a
n
d
p
r
e
v
i
o
u
s
u
s
e
o
f
E
c
st
a
s
y.
T
h
e
d
ia
g
n
o
-

Fi
g.
2
Up
pe
r
an
ter
ior
oc
cl
us
al
ra
di
og
ra
ph
sh
o
ws
ev
id
en
ce
of
mi
ld
bl
un
tin
g
of
th
e
ro
ot
s
of

t ad
h e.
e
C
t
ess
e
e ati
t on
h of
b the
u use
t
of
n
M
o
sD
i M
gA
n wa
if s
i
ad
c
a vis
n ed,
t an
bd
o ora
nl
e
hy
l
o gie
s ne
s ed

uc
ati
on
pro
si
vid
s
o
ed.
f
Su
l
bo
c gin
a giv
l al
d de
r bri
u de
g me
i nt
n an
dd
u su
c pra
ed gin
n giv
e al
c sca
r lin
og
ti of
si the
n inv
g olv
g ed
i tee
n th
- wa
gs
i per
v for
it me
is d.
wFlu
a ori
s de
m[D
ura

p
h
at
2.
2
6
%
S
o
d
iu
m
f
l
u
o
ri
d
e
5
%
v
a
r
n
is
h
;
C
o
l
g
at
e
]
w
a
s
al
s
o
a
p
p
li
e
d
t
o
t
h
e
e
x
p
o
s
e
d
r
o
o
ts
t
o
r
el
ie
v
e
d

ent
inal
sen
siti
vit
y.
An
ort
ho
do
nti
c
ret
ain
er
wa
s
co
nst
ruc
ted
to
su
pp
ort
the
mo
bil
e
up
per
ant
eri
or
tee
th.
Th
e
mu
cos
al
ulc
er
ha
d
he
ale
d
at
1
we
ek
rev
ie
w
an
d4
mo
nth
s
aft
er
pre
sen
tati
on
the
tee
th
we
re

fi m
r m
masy
amp
n to
d ma
v tic
it loc
alali
. sed
T def
h ect
e of
p the
atalv
ieeol
n ar
t gin
atgiv
t ae
h an
is d
ti su
mpp
e ort
ha ing
d bo
n ne
o re
c ma
o ine
md,
p an
lad
i he
n wa
ts s
, dis
alch
t arg
h ed
o ba
u ck
g to
h his
a ge
2 ner
al
3 de
4
F
1E
9B
R
8U
BA
RR
IY
T2
I2
S2
H0
0
D3
E
N
T
A
L
J
O
U
R
N
A
L
V
O
L
U
M
E
1
9
4
N
O
.

n
ta
l
p
r
a
ct
it
i
o
n
e
r
f
o
r
r
e
g
u
la
r
p
e
ri
o
d
o
n
ta
l
m
ai
n
te
n
a
n
c
e.

D
I
S
C
U
S
S
I
O

N
M
D
M
A
is
wi
del
y
ac
ce
pte
d
wit
hin
the
ge
nera
l
po
pul
ati
on
as
a
rel
ati
vel
y
saf
e
dr
ug
an
d
is
be
co
mi
ng
mo
re
fre
qu
ent
ly
us
ed,

PRACTICE
e.
Th
e
ma
lai
d se
e an
sd
p fat
it ig
e ue
it re
s po
p rte
od
t in
e thi
ns
ti ca
a se
ll is
y sai
sd
e to
ri oc
o cu
ur
s wi
sithi
dn
e ho
e urs
ffor
e da
c ys
tsof
. M
TD
hM
eA
s us
e 9
a e.
r Th
ee
n bl
o oo
t d
r bi
e oc
l he
a mi
t str
ey
d pr
t ofi
o le
t wi
h th
e mi
d ldl
oy
s ele
e vat
o ed
r en
frzy
e me
-s
q co
u nfi
e rm
ns a
c he
y pat
o iti
fc
u pic
s tur

e
c
o
n
si
st
e
n
t
w
it
h
M
D
M
A
u
s
e.
T
h
e
ti
m
e
i
n
t
e
r
v
a
l
b
e
t
w
e
e
n
d
r
u
g
u
s
e
a
n
d
o
n
s
e
t
o
f
s
y
m
p
t
o
m
s
is
c
o
n
si
st
e
n
t
w
it
h

ac
ute
eff
ect
s
of
M
D
M
A.
T
her
e
ha
ve
be
en
no
pre
vio
us
rep
ort
s
of
ora
l
mu
co
sal
or
per
iod
ont
al
les
ion
s
ass
oci
ate
d
wit
h
ab
us
e
of
M
D
M
A,
alt
ho
ug
h
si
mi
lar
les
ion
s
to
tho
se
see
n
in
thi
s
cas
e
ha
ve
be
en
rep
ort
ed

w0
it 12
h
t wh
h ich
e oc
l cu
or
c fol
a lo
l wi
a ng
p ch
p ro
li nic
c gi
a ng
ti iva
ol
n ap
o pli
f cat
c io
o n.
c Th
a is
i is
n th
e ou
. gh
Tt
h to
e oc
s cu
er
i as
na
c res
l ult
u of
d the
e isc
g ha
i em
n ic
g va
i so
v co
a nst
l ric
a tin
ng
d act
mio
un
c of
o the
s dr
a ug.
l 12,
u 13
l
c Ce
e rvi
r cal
a ab
ti ras
o io
n ns
a an
nd
d gi
p ng
e iva
ri l
o lac
d era
o tio
n ns
ti ha
ti ve
s als
1o
be

e
n
d
e
s
c
ri
b
e
d
a
n
d
a
r
e
t
h
o
u
g
h
t
t
o
b
e
t
h
e
r
e
s
u
lt
o
f
e
x
c
e
s
si
v
e
t
o
o
t
h
b
r
u
s
h
i
n
g
d
u
ri
n
g
a

h
i
g
h
.
1
4

T
h
is
p
a
ti
e
n
t
r

ep
ort
ed
tha
t
he
sto
red
M
D
M
A
in
the
up
per
ve
sti
bul
e.
Th
is
wa
s
un
us
ual
as
the
dr
ug
is
us
ual
ly
ing
est
ed
ora
lly
im
me
dia
tel
y,
unl
ike
co
cai
ne
wh
ich
wh
en
ru
bb
ed
int
o
the
ora
l
mu
co
sa
is
we
ll
ab
sor
be
d.
T
he
lab
ial
mu
co
sa
adj
ac
ent

t
o
t
h
e
a
r
e
a
o
f
d
r
u
g
a
p
p
li
c
a
ti
o
n
w
a
s
n
o
t
a
ff
e
c
t
e
d
.
T
h
is
m
i
g
h
t
b
e
d
u
e
t
o
:

1
Dif
f
e
r
e
n
t
m
u
c
o
s
a
l
t
y
p

e
s

t
h
e
f
i
r
m
l
y
a
t
t
a
c
h
e
d
a
l
v
e
o
l
a
r
m
u
c
o
s
a
v
e
r
s
u
s
l
o
o
s
e
l
y

u
m
a
t
t
a
c
h
e
d
l
a
b
i
a
l
m
u
c
o
s
a
s
u
c
h
t
h
a
t
p
r
o
l
o
n
g
e
d
c
o
n
t
a
c
t
w
i
t
h
o
n
e
a
r
e
a
o
f
e
p
i
t
h
e
l
i
-

m
a
y
n
o
t
o
c
c
u
r
o
n
t
h
e
l
i
p

1
Ex
p
o
s
u
r
e
t
o
s
a
l
i
v
a
r
y
f
l
o
w

m
i
n
o
r
s
a
l
i
v
a
r
y
g
l
a

n
d
fl
o
w
f
r
o
m
t
h
e
u
p
p
e
r
li
p
m
i
g
h
t
w
a
s
h
a
w
a
y
c
h
e
m
i
c
a
l
ir
ri
t
a
n
t
s
b
e
tt
e
r
t
h
a
n
a
l
v
e
o
l
a
r
m
u
c
o
s
a

2
Me
t

h
o
d

o
s
a
b
o y
f t
h
e e
c ti
s p
t o
a f
s t
y h
e
a t
p o
p n
l g
i u
c e
a w
t h
i o
o s
n e
e
p
it
i h
f e
li
t u
h m
e
i
s
t m
a o
b r
l e
e k
t e
w r
e a
r ti
e n
i
h s
e e
l d
d ,
t
o h
n i
t s
o m
i
t g
h h
e t
n
a o
l t
v b
e e
o a
l ff
a e
r c
t
m e
u d
c a

n
d
w
o
u
l
d
s
h
i
e
l
d
t
h
e
l
i
p
f
r
o
m
t
h
e
p
r
e
s
u
m
e
d
c
h
e
m
i
c
a
l
b
u
r
n
.
P
arr
y
et
al.
10

rep
ort
ed
a
cas
e
of
a
14
ye

a sti
r-bu
o le
l an
dd
mpr
u es
lt ent
i ed
p wi
l th
ea
d cli
r nic
u al
g pic
a tur
be
u su
s gg
e est
r ive
wof
h ne
o cr
a oti
p sin
pg
li gi
e ng
d ivi
c tis,
o wi
c th
a eyt
i he
n ma
e an
ad
n ulc
d era
a tio
mn
p of
h the
e gi
t ng
a iva
madj
i ac
n ent
e to
s the
o sit
ne
t of
o dr
t ug
h ap
e pli
u cat
p io
p n.
e Th
r is
l wa
as
b th
i ou
a gh
l t
v to
e be

a
l
o
c
a
l
d
r
u
g
r
e
a
c
ti
o
n
c
a
u
s
e
d
b
y
c
o
c
a
i
n
e.
H
o
w
e
v
e
r,
t
h
e
p
a
ti
e
n
t
h
a
d
a
ls
o
u
s
e
d
M
D
M
A
i
n
t
h
e
s
a
m
e
w
a

y
but
loc
al
eff
ect
s
of
thi
s
dr
ug
we
re
not
co
nsi
der
ed.
Ju
ve
nil
e
per
iod
ont
itis
in
an
im
mu
no
su
ppre
sse
d
pat
ien
t
ca
n
pre
se
nt
wit
ha
si
mi
lar
cli
nic
al
pic
tur
e
but
thi
s
ex
pla
nat
ion
did
not
coi
nci
de
wit
h
the
cli
nic

a bu
l se
fi wh
n ich
d ma
i y
n pr
g es
s ent
i to
n the
t ge
h ne
isral
p de
a nta
ti l
e pr
n act
t. itio
ner
h . It
isis
c inc
a rea
s sin
e gl
ry
e lik
p ely
o tha
rt t
h de
i nti
g sts
h
li
g
h
ts
a
p
r
e
v
i
o
u
sl
y
u
n
r
e
p
o
rt
e
d
e
ff
e
c
t
o
f
M
D
M
A
a

w
il
l
e
n
c
o
u
n
t
e
r
p
a
ti
e
n
ts
w
h
o
a
b
u
s
e
t
h
e
s
e
r
e1.
c
r
e
a
ti
o
n
a
l
d
r
u
g
s.
T
h
is
p
a
p
e
r
h
i
g
h
li
g
h
ts
t
h
e
n
e
e2.
d

for
a
hig
h
ind
ex
of
sus
pic
ion
of
dr
ug
ab
us
e
on
pre
se
nta
tio
n
of
un
us
ual
per
iod
ont
al
co
ndi
tio
ns.
R
e
e
s
T
D.
O
ra
l
ef
fe
ct
s
of
dr
u
g
u
s
e.
C
rit
R
e
v
O
ra
l
Bi
ol
&
M
e
d
1
9
9
2;
3:
1
6
31
8
4.
Sha
nno

n e
Mt

n
e
,
(

E
c
s
t
a
s
y

)
.
L
a
n
c
e
t
1
9
9
2
;
3
4
0
:
3
8
4
3
8
7
.

.
Ma
et l
h .
yl
e C
n o
e n
di t
o e
x n
y t
ms
et
h o
a f
m
p
h E
et c
a s
mt

in a
e s
( y
M

D .
M

A L
, a
n
E
c
c
e
st
t
a
s

1
9
9
P
5
a
;
y
)

e
d

3
4
m
6
e
:
E

1
a
1
r
0
e
0
2
0
1
0
1
0;
0
1
1
6:
.
3
7

4.7- He
3 nry
8 J
0. A,

3.

Jef
W
fre
o ys
l K
f J,
f Da
wli
K ng
, S.
To
H xici
a ty
y an
d
A de
ath
Ws
fro
Mm
, 3,4
S me
h thy
e len
r edi
l ox
o ym
c eth
k am
ph
K eta
mi

5.

D
M
A
eff
ec
ts
an
d
to
xi
cit
y.
E
ur
P
sy
ch
iat
ry
20
00
;
15
:
28
729
4.

6.

B
u
r
g
e
s
s
C
,
O

D
o
n
o
h
o
e
A
,
G
i
l
l
M
.
A
g
o
n
y
a
n
d
e
c
s
t
a
s
y
:
a
r
e
v
i
e
w
o
f
M

M
i
l
l
o
s
e
v
i
c
A
,
A
g
r
a
w
a
l
N
,
R
e
d
f
e
a
r
n
P
J
e
t
a
l
.
T
h
e
o
c
c
u
r
r
e
n
c
e
o
f
t
o
o
t

h
w
e
a
r

9
;
2
7
:

i
n 2
8
u 3
s e 2
r 8
s 7
.
o
f

7.

M
urr
ay
M
C,
Wi
lso
n
N
H
(
F.
3
Ec
,
st
4
as
y
M
rel
e
at
t
ed
h
to
y
ot
l
h
e
we
n
ar.
e
Br
DD
i en
o t J
x 19
y 98
M;
e 18
t 5:
h 26
A 4.
E
c
s
t
a
s
y

8.mp D

h u
e x
t b
a ur
my
i A
n J.
e E
cs
)
ta
.

sy

C
D
o
e
m
nt
m
al
u
i
n
m
i
pli
t
c
y

at
io
D
n
e
s.
n B
t r
D
Oe
r nt
a J
l 1
9
E 9
p 3;
i 1
d 7
e 5:
m3
i 8.

9.ol Mc

Ca
1 nn
9 U
9 D,

S
15:
l
10
a
7t
115
e
.
S
O
, Parry J,
Po
R
rte
i
r
c
S,
a
Sc
u
ull
rt
y
e
C
G
et
al.
A
Mu
.
co
A
sal
d
les
v
ion
e
s
r
du
s
e
e
to
r
ora
e
l
a
co
c
cai
ti
ne
o
us
n
e.
s
Br
w
De
it
nt
h
J
3
19
,
96;
4
18
0:
m
46
e
2t
46
h
4.
y

10.

11.L

l
e
n
e
d
i
o
x
y
m
e
t
h
a
m
p
h
e
t
m
i
n
e
(
M
D
M
A
:

E
c
s
t
s
y
)
.
D
r
u
g
S
a
f
1
9
9
6
;

e
e
C
Y
S
,
M
o
h
a
m
m
a
d
i
H
,
D
i
x
o
n
R
A
.
M
e
d
i
c
a
l
a
n
d
d
e

n
e
cr
o
si
s.
P
er
io
d
o
nt
al
C
a
s
e
R
e
p
1
9
8
5;
7:
4
44
5.

n A
t .
a
l C

i c
ma
p i
l n
i e
c
a p
t e
i r
o i
n o
s d

o n
f t
c
o
c
a
i
n
e
a
b
u
s
e
.

i
t
i
s
.

I
n
t
J

P
e
r
i
o
J d
o
On
r t
e

1
9
9
1
;
1
1
:

7
3
4
7
9
9
:
.
2

13.
9
0
Gargiulo
- A V,
2 Toto
9 P D,
3 Gar
. giul
oA
W.
Coc
Yuk aine
n indu
a ced
ging
R ival

12.

Garbino
J,
He
nry
J A,
Me
nth
aG
et
H
al.
,
Ecs
G
tas
o
y
r
ing
e
esti
li
on
c
and
k
ful
D
min
ant
A
hep
.
atic
D
fail
e
ure:
n
live
t
r
a
tran
l
spl
m
ant
a
n
atio
a
n to
g
be
e
con
m
sid
e
ere
n
da
t
last
o
ther
f
ape
t
utic
h
opti
e
on.
Vet
c
Hu
o
ma
c
n
a
Tox
i
icol
n
200
e
1;
43:
a
99d
102
d
i
.

Friedl
a
n
d
e
r
A

Ms
a t
x o
i r
l
l D
o e
f n
a t
c

1
9
9
1
;

1
9
8
8
;
6
5
:
4
5
4
8
.

15.

14.

a
l R

S
u
r
g

ct.
Or
al
Su
rg,
Or
al
M
ed
,
Or
al
Pa
th

BRITISH
DENTAL
JOURN
AL
VOLUM

E
1
9
4
N
O
.
4
F
E
B
R
U
A
R
Y
2
2
2
0
0
3
1
9
9