Methylone and mCPP, two new drugs of abuse?
ABSTRACT Recently, two new ecstasy-like substances, methylone and mCPP, were found in street drugs in the Netherlands by the Drugs Information and Monitoring System (DIMS). Methylone (3,4-methylenedioxymethcathinone) is the main ingredient of a new liquid designer drug that appeared on the Dutch drug market, called 'Explosion'. mCPP (meta-chlorophenylpiperazine) is a substance often used as a probe for the serotonin function in psychiatric research, and has now been found in street drugs, both in tablets and powders. Methylone as well as mCPP act on monoaminergic systems, resembling MDMA (3,4-methylenedioxymethamphetamine), with mCPP mainly affecting the serotonin system. The subjective effects of both new substances exhibit subtle differences with those of MDMA. Only little is known about the harmfulness of both methylone and mCPP. However, because of similarities between these substances and MDMA, risks common to MDMA cannot be excluded.
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ABSTRACT: Methylone, a new drug of abuse sold as "bath salts," has similar effects to ecstasy or cocaine. We have investigated changes in dopaminergic and serotoninergic markers, indicative of neuronal damage induced by methylone in the frontal cortex, hippocampus, and striatum of mice, according to two different treatment schedules. Methylone was given subcutaneously to male Swiss CD1 mice at an ambient temperature of 26 °C. Treatment A consisted of three doses of 25 mg/kg at 3.5-h intervals between doses for two consecutive days, and treatment B consisted of four doses of 25 mg/kg at 3-h intervals in 1 day. Repeated methylone administration induced hyperthermia and a significant loss in body weight. Following treatment A, methylone induced transient dopaminergic (frontal cortex) and serotoninergic (hippocampus) impairment. Following treatment B, transient dopaminergic (frontal cortex) and serotonergic (frontal cortex and hippocampus) changes 7 days after treatment were found. We found evidence of astrogliosis in the CA1 and the dentate gyrus of the hippocampus following treatment B. The animals also showed an increase in immobility time in the forced swim test, pointing to a depressive-like behavior. In cultured cortical neurons, methylone (for 24 and 48 h) did not induce a remarkable cytotoxic effect. The neural effects of methylone differ depending upon the treatment schedule. Neurochemical changes elicited by methylone are apparent when administered at an elevated ambient temperature, four times per day at 3-h intervals, which is in accordance with its short half-life.Psychopharmacology 04/2014; · 3.99 Impact Factor
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ABSTRACT: Characteristic ion mobility mass spectrometry data, reduced mobility, and limits of detection (signal-to-noise ratio = 3) were determined for six synthetic drugs and cocaine by ion mobility time-of-flight mass spectrometry (IM-TOF-MS) with electrospray ionization (ESI) and atmospheric pressure chemical ionization (APCI). The studied synthetic illicit drugs recently appeared on the recreational drug market as designer drugs and were methylone, 4-MEC (4'-methylethcathinone), 3,4-MDPV (3,4-methylenedioxypyrovalerone), JWH-210 [4-ethylnaphthalen-1-yl-(1-pentylindol-3-yl)methanone], JWH-250 [2-(2-methoxyphenyl)-1-(1-pentyl-1H-indol-3-yl)ethanone], and JWH-203 [1-pentyl-3-(2'-chlorophenylacetyl) indole]. Absolute reduced mobilities in nitrogen were 1.35, 1.28, 1.41, 1.30, 1.18, 0.98, 1.09, and 1.07 cm2V(-1)s(-1), for methylone [M-H]+, methylone [M+H]+, 4-MEC [M-H]+, 4-MEC [M+H]+, 3,4-MDPV [M+H]+, JWH-210 [M+H]+, JWH-250 [M+H]+, and JWH-203 [M+H]+, respectively. Selected illicit drugs are easily identified by IM-TOF-MS during a 100s analysis. Relative Limits of detection ranged from 4 to 400 nM are demonstrated for these compounds. Such relative limits of detection correspond to 14 pg to 2 ng absolute limits of detection. Better detection limits are obtained in APCI mode for all the illicit drugs except cocaine. ESI mode was found to be preferable for the IM-TOF-MS detection of cocaine at trace levels. A single sample analysis is completed in an order of magnitude less time than that for conventional liquid chromatography/mass spectrometry approach. The application allows one to consider IM-TOF-MS as a good candidate for a method to determine quickly the recently surfaced designer drugs marketed on the internet as "bath salts," "spice," and "herbal blends".European journal of mass spectrometry (Chichester, England). 01/2014; 20(2):185-92.
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ABSTRACT: Methylone is a cathinone derivative that has recently emerged as a designer drug of abuse in Europe and the USA. Studies on the acute and long-term neurotoxicity of cathinones are starting to be conducted. We investigated the neurochemical/enzymatic changes indicative of neurotoxicity after methylone administration (4 × 20 mg/kg, subcutaneously, per day with 3 h intervals) to adolescent rats, to model human recreational use. In addition, we studied the effect of methylone on spatial learning ad memory using the Morris water maze paradigm. Our experiments were carried out at a high ambient temperature to simulate the hot conditions found in dance clubs where the drug is consumed. We observed a hyperthermic response to methylone that reached a peak 30 min after each dose. We determined a serotonergic impairment in methylone-treated rats, especially in the frontal cortex, where it was accompanied by astrogliosis. Some serotonergic alterations were also present in the hippocampus and striatum. No significant neurotoxic effect on the dopaminergic system was identified. Methylone-treated animals only displayed impairments in the probe trial of the Morris water maze, which concerns reference memory, while the spatial learning process seemed to be preserved.Journal of Psychopharmacology 09/2014; · 2.81 Impact Factor
Methylone and mCPP, two new drugs of abuse?
M. G. BOSSONG, J. P. VAN DIJK & R. J. M. NIESINK
Drugs Information and Monitoring System (DIMS), Trimbos Institute for Mental Health and Addiction,
Utrecht, the Netherlands
Recently, two new ecstasy-like substances, methylone and mCPP, were found in street drugs in the
Netherlands by the Drugs Information and Monitoring System (DIMS). Methylone (3,4-
methylenedioxymethcathinone) is the main ingredient of a new liquid designer drug that appeared
on the Dutch drug market, called ‘Explosion’. mCPP (meta-chlorophenylpiperazine) is a substance
often used as a probe for the serotonin function in psychiatric research, and has now been found in street
drugs, both in tablets and powders. Methylone as well as mCPP act on monoaminergic systems,
resembling MDMA (3,4-methylenedioxymethamphetamine), with mCPP mainly affecting the
serotonin system. The subjective effects of both new substances exhibit subtle differences with those of
MDMA. Only little is known about the harmfulness of both methylone and mCPP. However, because
of similarities between these substances and MDMA, risks common to MDMA cannot be excluded.
Ever since ecstasy (XTC, MDMA) was classified as a
Schedule I drug, people have been trying to find non-
scheduled alternatives with effects matching those of ecstasy.
Examples of such ecstasy-like designer drugs are 4-MTA
(Winstock et al., 2002), MBDB (Carter et al., 2000) and
MDEA (Freudenmann & Spitzer, 2004). Recently, two new
ecstasy-like substances, methylone and mCPP, were detected
in street drugs in the Netherlands by the Drugs Information
and Monitoring System (DIMS). DIMS is a toxicoepidemio-
logic monitor of illegal drug markets. Its main focuses are to
identify the compounds of synthetic drugs, describe preva-
lence and trends, and identify health risks (Spruit, 2001).
At the end of 2004, a new designer drug called ‘Explosion’
appeared in the Netherlands. This new drug is sold as a liquid
via the internet and in Dutch ‘smartshops’, stores selling non-
scheduled (herbal) psychoactive substances. The product is
advertised as a ‘room odorizer’ and is sold in plastic tubes
containing 5ml of liquid. The tubes cost between e10 and e15
($13–$20) and do not present any information about the
composition of Explosion; they contain only a label saying
‘Room odorizer Vanilla. Do not ingest’ and ‘Keep away from
children. Never use more than one bottle’. In spite of this
label, users mention that they ingest the liquid to reach the
intended psychoactive effect. The text was probably put onto
the label to circumvent Dutch regulations for illicit drugs and
main ingredient of the liquid is the compound methylone
(3,4-methylenedioxymethcathinone or 2-methylamino-1-(3,4-
methcathinone (MDMCAT or MDMC) is the benzylic
ketone analogue of 3,4-methylenedioxymethamphetamine
(MDMA): it contains an additional oxygen atom at the
benzylic position of the molecule (Figure 1) (Cozzi et al.,
1999). 3,4-Methylenedioxymethcathinone was first synthe-
sized by Alexander Shulgin. Because of the similarity
of effects between methamphetamine and its benzylic
ketone methcathinone, he examined whether there was a
benzylic analogue. He called the new substance methylone
Methylone resembles MDMA in its behavioural profile, as
methylone substitutes for MDMA in rats trained to discrimi-
nate MDMA from saline. Methylone does not substitute for
amphetamine or for the hallucinogenic DOM in animals
trained to discriminate between these drugs and saline (Dal
Cason et al., 1997). Further, also in common with MDMA,
methylone acts on monoaminergic systems. In vitro, methy-
lone is threefold less potent than MDMA at inhibiting platelet
serotonin accumulation and as potent as MDMA in its
Correspondence to: Matthijs Bossong, MSc, Trimbos Institute for Mental Health and Addiction, PO Box 725, 3500 AS Utrecht,
The Netherlands. Tel: þ31 30 2971106; Fax: þ31 30 2971111; E-mail: email@example.com
Addiction Biology (December 2005) 10, 321–323
ISSN 1355-6215 print/ISSN 1369-1600 online/05/040321–03
ª Society for the Study of Addiction to Alcohol and Other Drugs
Taylor & Francis
inhibiting effects on the dopamine and noradrenaline trans-
porters (Cozzi et al., 1999).
In spite of these behavioural and pharmacological simila-
rities 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.
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 flecks, both types without a logo.
The dose of mCPP in the tablets ranged from 2 to 46mg. 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 detec-
tion of mCPP were received from Sweden, France, Austria
and Lithuania, 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 (Buydens-
Branchey 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 cytoplas-
matic 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 (2–46mg) 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 0.75mg/kg (7–52.5mg 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.
Figure 1. Molecular structures of 3,4-methylenedioxymethamfetamine
(MDMA) (a) and methylone (b).
M. G. Bossong et al.
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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New drugs of abuse