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Addiction B iology ( Mo n t h 2 0 0 5 ) 0 0 , 1 – 3
SHORT COMMUNICATION
Me t h y l o n e a n d m CP P , t w o n e w
d r u g s o f a b u s e ?
M. G. BOSSONG, J. P. VAN DIJK & R. J. M. NIESINK
Drugs Information and Monitoring System (DIMS), Trimbos Institute for Mental Health and Addiction,
U trecht, the N etherlands
Ab s t r a c t
R ecently, tw o new ecstasy- lik e substances, methylone and mC P P , w ere found in street drugs in the
N etherlands by the Drugs Information and Monitoring System (DIMS). Methylone (3 ,4 methylenediox ymethcathinone) is the main ingredient of a new liq uid designer drug that ap p eared
on the Dutch drug mark et, called ‘ E x p losion’ . mC P P (meta- chlorop henylp ip eraz ine) is a substance
often used as a p robe for the serotonin function in p sychiatric research, and has now been found in street
drugs, both in tablets and p ow ders. Methylone as w ell as mC P P act on monoaminergic systems,
resembling MDMA (3 ,4 - methylenediox ymethamp hetamine), w ith mC P P mainly affecting the
serotonin system. The subj ectiv e effects of both new substances ex hibit subtle differences w ith those of
MDMA. O nly little is k now n about the harmfulness of both methylone and mC P P . How ev er, because
of similarities betw een these substances and MDMA, risk s common to MDMA cannot be ex cluded.
In t r o d u c t i o n
Ev e r s i n c e e c s t a s y ( X T C , MDMA) w a s c l a s s i fi e d a s a
Sc h e d u l e I d r u g , p e o p l e h a v e b e e n t r y i n g t o fi n d n o n s c h e d u le d a lte r n a tiv e s w ith e ffe c ts m a tc h in g th o s e o f e c s ta s y .
Ex a m p l e s o f s u c h e c s t a s y - l i k e d e s i g n e r d r u g s a r e 4 - MT A
( W i n s t o c k e t a l ., 2 0 0 2 ) , MBDB ( C a r t e r e t a l ., 2 0 0 0 ) a n d
MDEA ( F r e u d e n m a n n & Sp i t z e r , 2 0 0 4 ) . Re c e n t l y , t w o n e w
e c s t a s y - l i k e s u b s t a n c e s , m e t h y l o n e a n d m C PP, w e r e d e t e c t e d
i n s t r e e t d r u g s i n t h e Ne t h e r l a n d s b y t h e Dr u g s In f o r m a t i o n
a n d Mo n i t o r i n g Sy s t e m ( DIMS) . DIMS i s a t o x i c o e p i d e m i o l o g i c m o n i t o r o f i l l e g a l d r u g m a r k e t s . It s m a i n f o c u s e s a r e t o
id e n tify th e c o m p o u n d s o f s y n th e tic d r u g s , d e s c r ib e p r e v a l e n c e a n d t r e n d s , a n d i d e n t i f y h e a l t h r i s k s ( Sp r u i t , 2 0 0 1 ) .
3 , 4 - Me t h y l e n e d i o x y m e t h c a t h i n o n e : m e t h y l o n e
At t h e e n d o f 2 0 0 4 , a n e w d e s i g n e r d r u g c a l l e d ‘ Ex p l o s i o n ’
a p p e a r e d i n t h e Ne t h e r l a n d s . T h i s n e w d r u g i s s o l d a s a l i q u i d
v i a t h e i n t e r n e t a n d i n Du t c h ‘ s m a r t s h o p s ’ , s t o r e s s e l l i n g n o n s c h e d u le d ( h e r b a l) p s y c h o a c tiv e s u b s ta n c e s . T h e p r o d u c t is
a d v e r tis e d a s a ‘r o o m o d o r iz e r ’ a n d is s o ld in p la s tic tu b e s
c o n t a i n i n g 5 m l o f l i q u i d . T h e t u b e s c o s t b e t w e e n e1 0 a n d e1 5
( $ 1 3 – $ 2 0 ) a n d d o n o t p r e s e n t a n y in fo r m a tio n a b o u t th e
c o m p o s i t i o n o f Ex p l o s i o n ; t h e y c o n t a i n o n l y a l a b e l s a y i n g
‘ Ro o m o d o r i z e r Va n i l l a . Do n o t i n g e s t ’ a n d ‘ Ke e p a w a y f r o m
c h i l d r e n . Ne v e r u s e m o r e t h a n o n e b o t t l e ’ . In s p i t e o f t h i s
la b e l, u s e r s m e n tio n th a t th e y in g e s t th e liq u id to r e a c h th e
in te n d e d p s y c h o a c tiv e e ffe c t.T h e te x t w a s p r o b a b ly p u t o n to
t h e l a b e l t o c i r c u m v e n t Du t c h r e g u l a t i o n s f o r i l l i c i t d r u g s a n d
p s y c h o a c tiv e s u b s ta n c e s .
An a l y s e s o f Ex p l o s i o n
h a v e d e m o n stra te d
th a t th e
m a in in g r e d ie n t o f th e liq u id is th e c o m p o u n d m e th y lo n e
( 3 ,4 - m e t h y l e n e d i o x y m e t h c a t h i n o n e o r 2 - m e t h y l a m i n o - 1 - ( 3 ,4 m e t h y l e n e d i o x y p h e n y l ) p r o p a n - 1 - o n e ) . 3 ,4 - Me t h y l e n e d i o x y m e t h c a t h i n o n e ( MDMC AT o r MDMC ) i s t h e b e n z y l i c
k e t o n e a n a l o g u e o f 3 ,4 - m e t h y l e n e d i o x y m e t h a m p h e t a m i n e
( MDMA) : i t c o n t a i n s a n a d d i t i o n a l o x y g e n a t o m
a t th e
b e n z y l i c p o s i t i o n o f t h e m o l e c u l e ( F i g u r e 1 ) ( C o z z i e t a l .,
1 9 9 9 ) . 3 ,4 - Me t h y l e n e d i o x y m e t h c a t h i n o n e w a s fi r s t s y n t h e s i z e d b y Al e x a n d e r Sh u l g i n . Be c a u s e o f t h e s i m i l a r i t y
o f e ffe c ts b e tw e e n m e th a m p h e ta m in e a n d its b e n z y lic
k e to n e m e th c a th in o n e , h e e x a m in e d w h e th e r th e r e w a s a
c o m p a r a b le
c o n n e c tio n
b e tw e e n
MDMA a n d
its
b e n z y lic a n a lo g u e . H e c a lle d th e n e w s u b s ta n c e m e th y lo n e
( C o g n i t i v e l i b e r t y .o r g ) .
Me t h y l o n e r e s e m b l e s MDMA i n i t s b e h a v i o u r a l p r o fi l e , a s
m e t h y l o n e s u b s t i t u t e s f o r MDMA i n r a t s t r a i n e d t o d i s c r i m i n a t e MDMA f r o m s a l i n e . Me t h y l o n e d o e s n o t s u b s t i t u t e f o r
a m p h e t a m i n e o r f o r t h e h a l l u c i n o g e n i c DOM i n a n i m a l s
t r a i n e d t o d i s c r i m i n a t e b e t w e e n t h e s e d r u g s a n d s a l i n e ( Da l
C a s o n e t a l ., 1 9 9 7 ) . F u r t h e r , a l s o i n c o m m o n w i t h MDMA,
m e t h y l o n e a c t s o n m o n o a m i n e r g i c s y s t e m s . In v itro, m e t h y l o n e i s t h r e e f o l d l e s s p o t e n t t h a n MDMA a t i n h i b i t i n g p l a t e l e t
s e r o t o n i n a c c u m u l a t i o n a n d a s p o t e n t a s MDMA i n i t s
C o r r e s p o n d e n c e t o : Ma t t h i j s Bo s s o n g , MSc , T r i m b o s In s t i t u t e f o r Me n t a l H e a l t h a n d Ad d i c t i o n , PO Bo x
T h e Ne t h e r l a n d s . T e l : þ3 1 3 0 2 9 7 1 1 0 6 ; F a x : þ3 1 3 0 2 9 7 1 1 1 1 ; E- m a i l : m b o s s o n g @ t r i m b o s .n l
ISSN 1 3 5 5 - 6 2 1 5 p r i n t / ISSN 1 3 6 9 - 1 6 0 0 o n l i n e / 0 5 / 0 0 0 0 0 1 – 0 3
ª So c i e t y f o r t h e St u d y o f Ad d i c t i o n t o Al c o h o l a n d Ot h e r Dr u g s
DOI: 1 0 .1 0 8 0 / 1 3 5 5 6 2 1 0 5 0 0 3 5 0 7 9 4
7 2 5 , 3 5 0 0
AS U t r e c h t ,
T a y lo r &F r a n c is
2
M. G . Bossong et al.
F igure 1 .
Molecular structures of 3,4-methylenedioxymethamfetamine
(MDMA) (a) and methylone (b).
inhibiting effects on the dopamine and noradrenaline transporters (Cozzi et al., 1999).
In spite of these behavioural and pharmacological similarities between methylone and MDMA, the observed subjective
effects of both drugs of abuse are not completely identical
(Erowid.org). Shulgin wrote about the effects of this drug:
‘methylone has almost the same potency of MDMA, but it
does not produce the same effects. It has an almost
antidepressant action, pleasant and positive, but not the
unique magic of MDMA’ (Cognitiveliberty.org).
In the Netherlands, methylone is not yet scheduled as a
drug of abuse, but is considered to be a psychoactive
medicine. Because methylone is not registered officially, as
such, it is forbidden to trade in methylone. The Minister of
Health has asked the Coordination point Assessment and
Monitoring new drugs group (CAM) to gather information
about this substance, resulting possibly in an official risk
assessment (van Amsterdam et al., 2004). Until now, no
research has been conducted on the toxicity of methylone, so
nothing is known about the harmfulness of this new drug.
Meta-chlorophenylpiperazine: mCPP
In September 2004, another ecstasy-like drug appeared on the
Dutch drug market: meta-chlorophenylpiperazine (mCPP).
mCPP is a pharmacologically active metabolite of the
antidepressant drugs trazodone, nefazodone and etoperidone
and of the minor tranquillizer mepiprazole (Rotzinger et al.,
1998). Its chemical name is 1-(3-chlorophenyl)piperazine and
the chemical formula is C10H13ClN2 (Reynolds, 1996).
From September 2004 until April 2005, DIMS registered
mCPP 25 times in drugs sold mainly as ecstasy, both in tablets
and powders. Two different kinds of tablets containing mCPP
were found: a beige-coloured, round-shaped tablet and a
white tablet with coloured fl ecks, both types without a logo.
The dose of mCPP in the tablets ranged from 2 to 46 mg. In
three cases, mCPP was discovered in a powder. Two powders
were sold as cocaine and one as speed, containing 7% , 8% and
5% mCPP, respectively, the first-mentioned in combination
with 1% cocaine-HCl. In addition to these identifications of
mCPP in the Netherlands, mCPP has also been detected in
several other European countries. Notifications of the detection of mCPP were received from Sweden, France, Austria
and L ithuania, via the European Monitoring Centre for Drugs
and Drug Addiction (EMCDDA). Further, mCPP can be
bought on the internet as X4, a tablet containing a
combination of four types of piperazines (mCPP, TFMPP,
oMPP and pCPP) (Naturensdroger.nu; Modernatur.nu).
mCPP is the most extensively used probe of serotonin
function in psychiatric research (Kahn & Wetzler, 1991). It has
both pre- and postsynaptic effects on the serotonin system.
First, mCPP induces a release of serotonin (5-HT) dependent
on the serotonin transporter (SERT) (Pettibone & Williams,
1984; Baumann et al., 1993, 2001; Eriksson et al., 1999;
Gobbi et al., 2002). Secondly, mCPP possesses agonist
properties at some 5-HT receptors (e.g. 5-HT2C) and
antagonist properties at others (e.g. 5-HT2B) (Hamik &
Peroutka, 1989; Thomas et al., 1996; Gijsman et al., 2004).
Concerning these effects on the serotonin system, mCPP is a
substance partially comparable with MDMA, as MDMA
releases 5-HT via a SERT-mediated process as well (e.g.
Rudnick & Wall, 1992; for a review see Cole & Sumnall,
2003). As a consequence, the subjective effects of mCPP and
MDMA are also comparable, both positive as well as negative
(Tancer & Johanson, 2001, 2003). Examples of mild side
effects mentioned after the use of mCPP are anxiety, dizziness
and confusion (Gijsman et al., 1998; Tancer & Johanson,
2001, 2003; Feuchtl et al., 2004), whereas migraine and panic
attacks are observed frequently as severe negative effects
(Gijsman et al., 1998, 2004). Interestingly, MDMA-users
(McCann et al., 1999) and cocaine addicts (BuydensBranchey et al., 1997) report a more positive response to
mCPP than non-drug using volunteers.
An important difference between mCPP and MDMA is the
effect on the dopamine system: mCPP only exhibits minimal
effects on this system (Baumann et al., 2001; Gobbi et al.,
2002). Therefore, mCPP does not display any reinforcing
effects (Tancer & Johanson, 2003). Probably, in contrast with
MDMA, heart rate, blood pressure and body temperature are
only mildly increased following the use of mCPP (Ghaziuddin
et al., 2003; Tancer & Johanson, 2003), while both mCPP and
MDMA cause a dose-dependent elevation of the hormones
ACTH, cortisol and prolactin (Kahn & Wetzler, 1991;
Gijsman et al., 1998; Ghaziuddin et al., 2003; Feuchtl et al.,
2004). Physiological and subjective effects reach their peak
after 1 – 2 hours after oral administration (Tancer & Johanson,
2001, 2003). The effects can last 4 – 8 hours (Gijsman et al.,
1998; Tancer & Johanson, 2001, 2003).
While MDMA is known to be a neurotoxic compound,
mCPP lacks neurotoxic potential (Gobbi et al., 2002). mCPP
is able to release 5-HT without causing a long-term depletion
of 5-HT (Ulrichsen et al., 1992; Baumann et al., 2001).
Possibly, this difference between MDMA and mCPP can be
explained by the fact that mCPP releases only the cytoplasmatic 5-HT, while MDMA induces the release of both
cytoplasmatic and vesicular 5-HT (Gobbi et al., 2002).
The doses of mCPP found in the street drugs analysed by
DIMS (2 – 46 mg) are comparable with the doses used in
challenge tests of the serotonin system in psychiatry. In these
tests, the commonly used oral dose of mCPP ranges from 0.1
to 0.75 mg/kg (7 – 52.5 mg mCPP for a 70-kg person) (Tancer
& Johanson, 2001, 2003; Gijsman et al., 2004). However,
these are doses of individual tablets. When several tablets are
ingested, the clinically used dose can be exceeded. This might
result in the serotonin syndrome (Klaassen et al., 1998).
Therefore, the use of mCPP in combination with alcohol,
ecstasy or antidepressant drugs should be avoided.
In contrast with methylone, mCPP is registered officially.
Consequently, only licensed traders are allowed to sell this
substance. Because mCPP has appeared on the illegal drug
market, it might become subject to an official risk assessment
by the CAM.
New drugs of abuse
Until now, little has been known about the use and use
patterns of methylone and mCPP. Monitoring and specific
epidemiological research among high-risk users could gain an
insight into risks associated with the use of these drugs alone
or in combination with other drugs.
The abuse of methylone and mCPP have not yet been
reported to be associated with fatal or non-fatal intoxication.
However, both substances carry potential risks common to
MDMA and 4-MTA. Therefore, a risk of acute or chronic
toxicity cannot be excluded.
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