Methylone(bkMDMA)

CriticalReviewReport
Agendaitem4.14

ExpertCommitteeonDrugDependence
ThirtysixthMeeting
Geneva,1620June2014

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Acknowledgments
This report has been drafted under the responsibility of the WHO Secretariat, Essential
Medicines and Health Products, Policy Access and Rational Use Unit. The WHO Secretariat
would like to thank the following people for their contribution in producing this critical
review report: Wim Best, the Netherlands (literature review and drafting), Dr Caroline
Bodenschatz, Switzerland (editing) and Mr David Beran, Switzerland (questionnaire report
drafting).

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Contents
Summary..................................................................................................................................................................... 7
1.

Substance identification ................................................................................................................................... 8

A.
B.
C.
D.
E.
F.
G.

2.

International Nonproprietary Name (INN) ............................................................................................... 8

Chemical Abstract Service (CAS) Registry Number ................................................................................. 8
Other Names ............................................................................................................................................... 8
Trade Names............................................................................................................................................... 8
Street Names ............................................................................................................................................... 8
Physical properties ..................................................................................................................................... 8
WHO Review History ................................................................................................................................. 8

Chemistry ........................................................................................................................................................... 9
A.
B.
C.
D.
E.
F.
G.

Chemical Name .......................................................................................................................................... 9

Chemical Structure ..................................................................................................................................... 9
Stereoisomers ............................................................................................................................................. 9
Synthesis ..................................................................................................................................................... 9
Chemical description.................................................................................................................................. 9
Chemical properties ................................................................................................................................... 9
Chemical identification ............................................................................................................................ 10

3.

Ease of convertibility into controlled substances ........................................................................................ 10

4.

General pharmacology ................................................................................................................................... 10

4.1. Pharmacodynamics .................................................................................................................................. 10
4.2. Routes of administration and dosage....................................................................................................... 12
4.3. Pharmacokinetics ..................................................................................................................................... 13

5.

Toxicology ........................................................................................................................................................ 14

6.

Adverse reactions in humans ......................................................................................................................... 14

7.

Dependence potential ...................................................................................................................................... 16

8.

Abuse potential ................................................................................................................................................ 16

9.

Therapeutic applications and extent of therapeutic use and epidemiology of medical use ................... 17

10. Listing on the WHO Model List of Essential Medicines ............................................................................ 17

11. Marketing authorizations (as a medicine) ................................................................................................... 17
12. Industrial use ................................................................................................................................................... 17
13. Non-medical use, abuse and dependence ..................................................................................................... 17
14. Nature and magnitude of public health problems related to misuse, abuse and dependence .............. 17
15. Licit production, consumption and international trade ............................................................................. 18
16. Illicit manufacture and traffic and related information ............................................................................ 18
17. Current international controls and their impact ........................................................................................ 19
18. Current and past national controls ............................................................................................................... 19
19. Other medical and scientific matters relevant for a recommendation on the scheduling of the
substance .......................................................................................................................................................... 19
References ................................................................................................................................................................. 21
Annex 1: Report on WHO Questionnaire for Review of Psychaoctive Substances for the 36th ECDD:
Evaluation of Methylone ................................................................................................................................ 23

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Summary
Methylone ((3,4-methylenedioxy)methcathinone) is a synthetic cathinone. It is the beta-keto
version of 3,4-methylenedioxymethylamphetamine (mdma). It was originally developed as a
therapeutic for Parkinsons disease or depression by Shulgin. Use of methylone was first
reported around 2005. Use/abuse has been reported from Japan, the USA and Europe. The
effects and the mode of use reported have similarities with mdma, but its potency is less.
Reported toxic effects of methylone include tachycardia, hypertension, paranoia, anxiety,
bruxism and muscle tension and aching. Some of these effects leeding to hospital admissions.
A number of analytically confirmed drug-related deaths have been reported.
Animal studies have indicated that methylone possesses an abuse or dependence potential but
there are no human clinical data to support this.

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1. Substanceidentification
A.

International Nonproprietary Name (INN)

Not applicable

B.

Chemical Abstract Service (CAS) Registry Number

186028-79-5N (base, racemic mixture)
191916-41-3 (base, + stereo-isomer)
186028-80-8 (hydrochloride salt)

C.

Other Names
Methylone, 2-methylamino-1-(3,4-methylenedioxyphenyl)propan-1-one,
(3,4-methylenedioxy)methcathinone, bk-mdma, mdmc,
-keto-(3,4-methylenedioxyphenyl,N-methylamphetamine).

D.

Trade Names
None.

E.

Street Names
Only a limited number of street names for methylonen can be found in the
literature, like:
Ease, Explosion, Inpact, mdmcat. bk-MDMA, M1, Neocor, Room odorizer.

F.

Physical properties
Methylone hydrochloride salt is a white or lightly coloured powder.

G.

WHO Review History

Methylone was not previously pre-reviewed or critically reviewed. A direct
critical review is proposed based on information brought to WHOs attention that
Methylone is clandestinely manufactured, of especially serious risk to public
health and society, and of no recognized therapeutic use by any party. Preliminary
data collected from literature and different countries indicated that this substance
may cause substantial harm and that it has no medical use.

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2. Chemistry
A.

Chemical Name
IUPAC Name: (RS)- 2-methylamino-1-(3,4-methylenedioxyphenyl)propan-1-one
CA Index Name:
methylone

B.

Chemical Structure
Free base:

Molecular Formula: C11H13NO3

Molecular Weight:
207.23 g/mol
C.

Stereoisomers
Methylone contains a chiral centre at the C-2 carbon of the propane sidechain, so
that two enantiomers exist: R-methylone and S-methylone.
Due to the similarity with 3,4-methylenedioxymethylamphetamine (MDMA) the
S form is thought to be more potent than the R form.

D.

Synthesis
A ring-substituted N-methylcathinone derivative, like methylone, is best
synthesised by reacting the suitably substituted bromopropiophenone with
methylamine; the result is always racemic. In the case of methylone, for example,
2-bromo-3,4-methylenedioxy-propiophenone can be prepared by reacting 3,4methylenedioxypropiophenone with bromine.

E.

Chemical description
Methylone ((3,4-methylenedioxy)methcathinone) is a ring-substituted beta-ketoamphetamine related to methcathinone and 3,4-methylenedioxymetamphetamine
(MDMA).

F.

Chemical properties
Methylone hydrochloride salt is a white or lightly coloured powder. The powder
is readily soluble in water.

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G.

Chemical identification
Gas-chromatography mass-spectrometry (GC-MS) and liquid chromatography
with mass spectrometry-mass spectrometry (LC-MS/MS) techniques have been
developed for the detection of methylone (Fornal, 2013, Reitzel et al., 2012).
Methylone does not give a colour reaction with the Marquis test.

3. Easeofconvertibilityintocontrolledsubstances
Methylone is not converted into controlled substances.

4. Generalpharmacology
4.1.

Pharmacodynamics

In the mid-1990s methylone (mdmc) has been synthesized by Jacob and Shulgin
(1996) as a potential treatment for Parkinsons disease and for depression.
Methylone is the beta-keto analog of N-methyl-1-(3,4-methylenedioxyphenyl)-2aminopropane (mdma). The effects are comparable to mdma, for instance stimulation,
euphoria, empathogenic and entactogenic, but slighly milder.
Biochemical effects
Cozzi et al. (1999) tested the neurotransmitter uptake inhibition in vitro of
methylone.The beta-ketone was threefold less potent than the nonketo drug MDMA, at
inhibiting platelet serotonin accumulation, with IC(50) of 5.8+/-0.7 microM. Methylone
was similar in potency to MDMA at catecholamine transporters individually expressed
in transfected glial cells. For dopamine uptake, IC(50) was 0.82+/-0.17 microM,
respectively; for noradrenaline uptake, IC(50) value was 1. 2+/-0.1 microM,
respectively. In chromaffin granules, IC(50) for serotonin accumulation was 166+/-12
microM for methylone, 10-fold higher than the respective value for MDMA. The results
indicate that methylone potently inhibit plasma membrane catecholamine transporters
but only weakly inhibit the vesicle transporter.
Simmler et al. (2013) determined the potencies of several cathinones to inhibit DA, NA
and 5-HT transport into transporter-transfected HEK 293 cells, DA and 5-HT efflux
from monoamine-preloaded cells.
Methylone, mephedrone, ethylone, butylone and naphyrone act as non-selective
monoamine uptake inhibitors, similar to cocaine. Methylone, mephedrone, methylone,
ethylone and butylone also induce the release of 5-HT, similar to MDMA. All the
cathinones showed high blood-brain barrier permeability in an in vitro model;
mephedrone and MDPV exhibited particularly high permeability.
Sogawa et al. (2011) examined the effects of methylone on the transporters for
dopamine (DAT), norepinephrine (NET), and serotonin (SERT), using a heterologous
expression system in CHO cells.Methylone inhibited the activities of DAT, NET, and
SERT, in a concentration-dependent fashion with a rank order of NET > DAT > SERT.
Methylone was less effective at inhibiting DAT and NET, but more effective against

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SERT than was methamphetamine. The ability of methylone to inhibit monoamine

transporter function, probably by acting as a transportable substrate, underlies the
synergistic effect of methylone and methamphetamine.
In vitro studies using recombinant human monoamine transporters point in the same
direction (Eshleman et al., 2013). Mephedrone and methylone had higher inhibitory
potency at uptake compared to binding and generally induced release of preloaded
[H]neurotransmitter from human dopamine (hDAT), serotonin (hSERT) and
norepinephrine (hNET) transporters (highest potency at hNET), and thus are transporter
substrates, similar to methamphetamine and mdma. In general these substituted
methcathinones had low uptake inhibitory potency and low efficacy at inducing release
via human vesicular monoamine transporters (hVMAT2). Furthermore these
compounds were low potency h5-HT(1A) receptor partial agonists, h5-HT(2A) receptor
antagonists, weak h5-HT(2C) receptor antagonists and have no affinity for dopamine
receptors.
The primary mechanisms of action may be as inhibitors or substrates of DAT, SERT
and NET.
Also in vivo methods employed by Baumann et al. (2012) showed similar results.
Methylone is a weak motor stimulant when compared with methamphetamine.
Repeated administrations of mephedrone or methylone (3.0 and 10.0 mg/kg, s.c., 3
doses) caused hyperthermia but no long-term change in cortical or striatal amines,
whereas similar treatment with MDMA (2.5 and 7.5 mg/kg, s.c., 3 doses) evoked robust
hyperthermia and persistent depletion of cortical and striatal 5-HT.
Behavioral effects
Lpez-Arnau et al. (2012) recorded locomotor activity in mice following different doses
of cathinones (butylone, mephedrone and methylone).
All three cathinones (5-25 mg/kg ) caused hyperlocomotion, which was prevented with
ketanserin or haloperidol. Methylone was the most potent compound inhibiting both
[(3) H]5-HT and [(3) H]dopamine uptake with IC(50) values that correlate with its
affinity for dopamine and 5-HT transporter. The affinity of cathinones for 5-HT(2A)
receptors was similar to that of MDMA.
Butylone and methylone induced hyperlocomotion through activating 5-HT(2A)
receptors and increasing extra-cellular dopamine. They inhibited 5-HT and dopamine
uptake by competing with substrate. Methylone was the most potent 5-HT and
dopamine uptake inhibitor and its effect partly persisted after withdrawal.
Den Hollander et al. (2013) treated mice with a binge-like regimen of methylone (30
mg/kg, twice daily for 4 days) in order to investigate the possible long-term effects of
this drugs on a range of behavioral tests. Starting 2 weeks later, they performed
behavioral tests of memory, anxiety and depression. Methylone had little effect on
behavior or neurotransmitter levels in mice but produced a widespread depletion of 5HT and 5-HTT levels in rats.
Marusich et al. (2012) evaluated the in vivo effects of several synthetic cathinones and
compared them to those of cocaine (COC) and methamphetamine (METH). Acute
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effects of methylenedioxyphyrovalerone, mephedrone, methylone, methedrone, 3fluoromethcathinone, 4-fluoromethcathinone, COC, and METH were examined in male
ICR mice on locomotor activity, rotorod, and a functional observational battery (FOB).
All drugs increased locomotor activity, with different compounds showing different
potencies and time courses in locomotor activity. Methylone decreased performance on
the rotorod. The FOB showed that in addition to typical stimulant induced effects, some
synthetic cathinones produced ataxia, convulsions, and increased exploration. These
results suggest that individual synthetic cathinones differ in their profile of effects, and
differ from known stimulants of abuse.
4.2.

Routes of administration and dosage

Methylone can be administered through a variety of different routes, including oral,

intranasal, intravenous, sublingual, and rectal administration.
However oral consumption appears to be the most popular route of administration
(Erowid).
Intranasal dosage is the same as oral dosage but is not considered as rewarding and with
a much shorter duration of action.
Methylone is generally available as pure crystals but also oral solutions are available
(e.g. Explosion).
Oral dosages of methylone and activity:
Threshold
60 - 120 mg
Light
100 - 150 mg
Common
100 - 250 mg
Strong
160 - 270 mg
Very strong
250 + mg
Some users mention that increasing doses of methylone beyond 100-180 mg causes
increased physical effects but does not substantially improve the empathic cognitive
effects.
Timecourse of effects after oral dosages of methylone:
Onset
15 - 60 minutes
Coming Up
30 - 45 mins
Plateau
60 - 90 mins
Coming Down
60 - 120 mins
Duration
2 - 3.5 hours
Normal After Effects 6 - 24 hours
Total Duration
3 - 5 hrs
Bumping / boosting:
Methylone is sometimes used with a larger "attack" dose (first dose) and then smaller
"bumps" to maintain the effects for a longer period.
These bumps are taken orally or insufflated and are often around 30 - 100 mg oral and
20-80 mg insufflated.
A re-dose of a third to a half of the normal dose usually extends the duration for another
hour, a full-dose redose often extends the duration for another 1-2 hours.

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4.3.

Pharmacokinetics

Lpez-Arnau et al. (2013) investigated the pharmacokinetics of methylone in rats. In

order to provide a pharmacokinetic/pharmacodynamic model they also looked at the
locomotor activity of the animals.
Methylone was administered to male Sprague-Dawley rats intravenously (10mg/kg) and
orally (15 and 30 mg/kg). Plasma concentrations and metabolites were characterized by
LC/MS and LC-MS/MS fragmentation patterns. Locomotor activity was monitored for
180-240 min.
The plasma concentrations after i.v. administration fit a two-compartment model.
After oral administration, peak methylone concentrations were achieved between 0.5
and 1h. The absolute bioavailability was about 80% and the percentage of methylone
protein binding was of 30%.
They have identified four Phase I metabolites after oral administration. The major
metabolic routes are N-demethylation, aliphatic hydroxylation and O-methylation of a
demethylenate intermediate. A relationship between methylone brain levels and free
plasma concentration yielded a ratio of 1.42 0.06. Methylone induced a dosedependent increase in locomotor activity. The pharmacokinetic-pharmacodynamic
model successfully describes the relationship between methylone plasma concentrations
and its psychostimulant effect. A contribution of metabolites in the activity of
methylone after oral administration is suggested.
Kamata et al. (2006) investigated the urinary metabolites of methylone in humans and
rats. They administered methylone to rats and then analysed the urine specimens.
Furthermore they also analysed the urine of some users. Th techniques used were gas
chromatography-mass spectrometry (GC-MS) and liquid chromatography-electrospray
ionization mass spectrometry (LC-ESI MS).
The following major metabolic pathways were found:
-

side-chain degradation by N-demethylation to the corresponding primary amine,

methylenedioxycathinone (MDC);
demethylenation followed by O-methylation of either a 3- or 4-OH group on the
benzene ring to produce 4-hydroxy-3-methoxymethcathinone (HMMC) or 3hydroxy-4-methoxymethcathinone (3-OH-4-MeO-MC). Of these metabolites,
HMMC was the most abundant in humans and rats. All formed metabolites were
conjugated.

The same group (Katagi et al., 2010) showed in a later study that also beta-keto
reduction to the corresponding amino alcohols, 3,4-methyledioxyephedrine and 3,4methyledioxypseudoephedrine took place.
Pedersen et al. (2013) showed that cytochrome P450 2D6 (CYP2D6) was the main
responsible enzyme for the in vitro Phase I metabolism of methylone, with minor
contributions from CYP1A2, CYP2B6, and CYP2C19.The major metabolite was
identified as dihydroxymethcathinone, and the minor metabolites were N-hydroxymethylone, nor-methylone, and dihydro-methylone.
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Forensic casework has been performed by Cawrse et al. (2012). They analysed four
postmortem cases for methylone, mephedrone and MDPV, with drug levels quantitated
in multiple biological matrices. All four cases had detectable levels of methylone, with
heart blood concentrations between 0.060 and 1.12 mg/L. Analysis of several tissue
samples shows that methylone does not sequester in a particular tissue type after death.
The average liver-to-blood ratio was 2.68. Two different extraction methods, as well as
analysis of derivatized and underivatized methylone, show that the drug is suitable for
analysis in either method.
Another case is published by McIntyre et al. (2013). They describe a 19-year-old
woman who was known to use drugs. She was found floating in the ocean 100 yards
from the beach. When last seen she had said to a friend that she was going to get in the
water. Autopsy findings were consistent with drowning. Postmortem blood initially
screened positive for methamphetamine and cannabinoids by ELISA and was
subsequently confirmed for methylone by a specific GC-MS SIM analysis following
solid-phase extraction. Concentrations found in the peripheral blood, central blood and
vitreous content were measured at 3.4 mg/L 3.4 mg/L, and 4.3mg/L, respectively.

5. Toxicology
There are no published pre-clinical safety data available concerning the toxicity,
reproductive impact and carcinogenic/mutagenic potential of methylone.

6. Adversereactionsinhumans
Adverse events
For drugs of abuse there is no formal registration system for adverse events.
Information can be obtained by surveys, by searching on internetfora and by collecting
information from national poison information services.
The following adverse events of methylone use have been mentioned:
Cardiovascular System:
Heart racing, palpitations,
Hypertension.
Central Nervous System:
Dizziness;
Paranoia, confusion;
Anxiety, fear;
Increased in body temperature;
Fatigue, loss of appetite.
Gastro-intestinal system:
Gastrointestinal discomfort;
Nausea, vomiting.
Musculoskeletal system:
Bruxism (teeth grinding), jaw tension;
Muscle tension and aching.
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Miscellaneous:
Increased perspiration
Serious adverse events
Boulanger-Gobeil et al. (2012) report a case of methylone and ethcathinone poisoning
with severe clinical toxicity.
A 22-year-old woman was brought to the emergency department following several
episodes of tonicoclonic seizures, a few hours after ingesting "legal ecstasy". The
patient needed intubation for recurrent seizures, and she was found to have severe
hyponatremia (120 mmol/L) that was corrected with hypertonic saline. Furthermore she
developed prolonged rhabdomyolysis (CK 34.537 U/L) that required a 6-day
hospitalisation.
The seizures and the hyponatremia may be explained by the MDMA-like characteristics
of methylone that may induce inappropriate secretion of antidiuretic hormone mediated
via the serotonin system. The prolonged period of rhabdomyolysis may also be
explained by excessive serotonin activity resulting in an increased motor hyperactivity.
Fatal intoxications
So far only a limited number of fatal intoxications with methylone have been reported,
most of them originating from the USA.
Pearson et al. (2012) presented three fatal intoxications of methylone. Blood was
analyzed with a routine alkaline liquid-liquid extraction and analyzed by gas
chromatography coupled with a mass spectrometer (GC-MS). Methylone was identified
by a full scan mass spectral comparison to an analytical standard of methylone. In all
three fatalities, the deceased exhibited seizure-like activity and elevated body
temperatures (103.9, 105.9 and 107F) before death. Two of the three cases also
exhibited metabolic acidosis. One of the three cases had prolonged treatment and
hospitalization before death with symptoms similar to sympathomimetic toxicity,
including metabolic acidosis, rhabdomyolysis, acute renal failure and disseminated
intravascular coagulation. Peripheral blood methylone concentrations in the three fatal
cases were 0.84, 3.3 and 0.56 mg/L. Their conclusion is that peripheral blood methylone
concentrations in excess of 0.5 mg/L may result in death due to its toxic properties,
which can include elevated body temperature and other sympathomimetic-like
symptoms.
Warrick et al. (2012) report a case of a 24-year-old female who ingested a capsule
containing methylone and butylone sold as "Ecstasy". The patient presented to the
emergency department, comatose febrile, tachycardic, tachypnic, and hypertensive. On
exam, she was diaphoretic, tremulous, hyperreflexic, and had sustained clonus. The
patient progressed to multi-system organ failure and ultimately expired. The
investigators obtained and analyzed both her urine and a capsule found on her person
similar to the capsules ingested. In both samples, laboratory analysis identified only
methylone and butylone.
Carbone et al. (2013) reported a case of sudden death related to methylone in a 19year-old man. This is the first reported case of sudden cardiac death associated with
methylone use.The amount of methylone detected postmortem (0.7 mg/L) is in line with
the concentrations described by Pearson et al. (2012).
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Kovcs et al. (2012) present a fatal case related to the consumption of methylone. A
16-year-old boy suddenly lost his consciousness in a party. Resuscitation was
unsuccessful. His previous history included cardiac malformation detected at infancy
and bronchial asthma diagnosed one year before his death. Signs of sudden cardiac
death were observed during autopsy. In addition, striated heart muscle damage was
observed, which could be due to the use of an amphetamine-like substance. Methylone
intake was proved in blood and liver extract using gas chromatography/mass
spectrometry. The concentrations found were .272 mg/L in the blood and 387 ng/g in
the liver.
Finally five cases to which methylone might have been contibuted have been reported
from the UK (personal communication John Corkery).

7. Dependencepotential
No data available.

8. Abusepotential
Bonano et al. (2014) examined the behavioral effects of ()-methcathinone, ()-3,4methylenedioxypyrovalerone
(MDPV),
()-3,4-methylenedioxymethcathinone
(methylone), and ()-4-methylmethcathinone (mephedrone) in rats using intracranial
self-stimulation (ICSS). Male Sprague-Dawley rats with electrodes targeting the medial
forebrain bundle responded for multiple frequencies of brain stimulation and were
tested in two phases. First, dose-effect curves for methcathinone (0.1-1.0 mg/kg),
MDPV (0.32-3.2 mg/kg), methylone (1.0-10 mg/kg), and mephedrone (1.0-10 mg/kg)
were determined. Second, time courses were determined for effects produced by the
highest dose of each compound.
MDPV, methylone, and mephedrone produced dose- and time-dependent increases in
low rates of ICSS maintained by low brain stimulation frequencies, but also produced
abuse-limiting depression of high ICSS rates maintained by high brain stimulation
frequencies. Efficacies to facilitate ICSS were methcathinone MDPV methylone >
mephedrone. Methcathinone was the most potent compound, and MDPV was the
longest acting compound.
Watterson et al. (2012) tried to determine the relative abuse liability of methylone by
employing intravenous self-administration (IVSA) and intracranial self-stimulation
(ICSS) paradigms in rats. They demonstrated that methylone (0.05, 0.1, 0.2, and 0.5
mg/kg/infusion) dose-dependently functions as a reinforcer, and that there is a
significant positive relationship between methylone dose and reinforcer efficacy.
Furthermore, responding during short access sessions (ShA, 2 hr/day) appeared more
robust than previous IVSA studies with MDMA. However, unlike previous findings
with abused stimulants (cocaine, methamphetamine), long access sessions (LgA, 6
hr/day) did not lead to escalated drug intake or increased reinforcer efficacy. Finally,
methylone produced a dose-dependent, but statistically non-significant, trend towards
reductions in ICSS thresholds. Together these results reveal that methylone may possess
an addiction potential similar to or greater than MDMA, yet patterns of selfadministration and effects on brain reward function suggest that this drug may have a
lower potential for abuse and compulsive use than prototypical psychostimulants.
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Gatch et al. (2013) tried to determine whether cathinone compounds stimulate motor
activity and have discriminative stimulus effects similar to those of cocaine and/or
methamphetamine.
3,4-Methylenedioxypyrovalerone
(MDPV),
methylone,
mephedrone, naphyrone, flephedrone, and butylone were tested for locomotor stimulant
effects in mice and subsequently for substitution in rats trained to discriminate cocaine
(10 mg/kg, intraperitoneally) or methamphetamine (1 mg/kg, intraperitoneally) from
saline. All compounds fully substituted for the discriminative stimulus effects of
cocaine and methamphetamine. MDPV and naphyrone produced locomotor stimulant
effects that lasted much longer than those of cocaine or methamphetamine.

9. Therapeuticapplicationsandextentoftherapeuticuseand
epidemiologyofmedicaluse
Not applicable.

10.ListingontheWHOModelListofEssentialMedicines
Methylone is not listed on the WHO Model List of Essential Medicines.

11.Marketingauthorizations(asamedicine)
Methylone has never been marketed as a medicinal product.

12.Industrialuse
Methylone has no industrial use.

13.Nonmedicaluse,abuseanddependence
Gonzlez et al. (2013) looked at the pattern of use of new psychoactive substances in a
group of Spanish research chemical (RC) users . A total of 230 users participated. The
most frequent RCs were hallucinogenic phenethylamines (2C-B 80.0%, 2C-I 39.6%)
and cathinones (methylone 40.1%, mephedrone 35.2%). The most frequent combination
of RC with other illegal drugs was with cannabis (68.6%). here is a specific RC user
profile with extensive knowledge and consumption of substances, using different
strategies to reduce risks associated to its consumption.
Also refer Annex 1: Report on WHO questionnaire for review of psychoactive
substances.

14.Natureandmagnitudeofpublichealthproblemsrelatedto
misuse,abuse anddependence
Caudevilla-Glligo et al. (2013) described the presence and composition of synthetic
cathinones in drug samples analyzed at a Drug Testing Service. Data were obtained
from samples delivered as, or containing cathinones, between January 2010 and June

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2012. Specimens were identified by combining thin layer chromatography and gas
chromatography associated with mass spectrometry. Two hundred and thirty-seven
(3.8%) of the 6199 samples were delivered as, or contained cathinones. 22 different
cathinones were detected, alone or in different combinations. Methylone (24.9%),
mephedrone (24.5%), 4-methylethcathinone (9.28%), and methylenedioxypyrovalerone
(6.8%) were the most common cathinones. These substances were also found in 80
(1.3%) of samples delivered allegedly containing drugs different from cathinones
(mdma, amphetamines, ketamine, etc). Cathinone derivatives were markedly present in
the Spanish drug market during the studied period.
Helander et al. (2013) collected information concerning the increasing use of new
psychoactive substances. A project called 'STRIDA' was started to monitor the
occurrence and trends of new psychoactive substances in Sweden. Another part of the
project focused on collecting information about the clinical symptoms, toxicity and
associated health risks of these new psychoactive substances. A liquid
chromatographic-tandem mass spectrometric multi-component method has been
developed, allowing for the determination of > 80 novel psychoactive compounds or
metabolites thereof.
In their study they focused mainly on the particular drug substances identified and the
population demographics of the initial STRIDA cases.
In urine and/or blood samples obtained from 103 consecutive cases of admitted or
suspected recreational drug intoxications in mostly young subjects (78% were 25
years, and 81% were males) presenting at emergency departments all over the country,
psychoactive substances were detected in 82%. The substances comprised synthetic
cannabinoids, substituted cathinones (e.g. butylone, MDPV and methylone) and
tryptamines, and also plant-based substances as well as conventional drugs-of-abuse. In
44% of the cases, more than one new psychoactive substance, or a mixture of new
and/or conventional drugs were detected.
Also refer Annex 1: Report on WHO questionnaire for review of psychoactive
substances.

15.Licitproduction,consumptionandinternationaltrade
There are no known uses of methylone as a research, industrial, agricultural or cosmetic
compound, despite it being marketed as room odorizer, bath salt or research
chemical.
Also refer Annex 1: Report on WHO questionnaire for review of psychoactive
substances.

16.Illicitmanufactureandtrafficandrelatedinformation
Refer Annex 1: Report on WHO questionnaire for review of psychoactive substances.

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17.Currentinternationalcontrolsandtheirimpact
Not applicable.

18. Currentandpastnationalcontrols
Refer Annex 1: Report on WHO questionnaire for review of psychoactive substances.

19.Othermedicalandscientificmattersrelevantfora
recommendationontheschedulingofthesubstance

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AE, Cozzi NV. The designer methcathinone analogs, mephedrone and methylone, are substrates for
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Bonano JS, Glennon RA, De Felice LJ, Banks ML, Negus SS. Abuse-related and abuse-limiting effects of
methcathinone and the synthetic "bath salts" cathinone analogs methylenedioxypyrovalerone (MDPV),
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Cawrse BM, Levine B, Jufer RA, Fowler DR, Vorce SP, Dickson AJ, Holler JM. Distribution of methylone in
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Gatch MB, Taylor CM, Forster MJ. Locomotor stimulant and discriminative stimulus effects of 'bath salt'
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Annex1:
ReportonWHOQuestionnaireforReviewofPsychaoctive
Substancesforthe36thECDD:EvaluationofMethylone
Data were obtained from 72 WHO Member States (18 AFR, 13 AMR, 5 EMR, 29 EUR,
3 SEAR, 4 WPR).
A total of 65 Member States answered the questionnaire for Methylone (bk-MDMA). Of
these, only 32 respondents (AMR 6, EUR 22, SEAR 1, WPR 3 ) had information on this
substance.
LEGITIMATE USE
None reported that methylone was currently authorized or is in the process of being
authorized/registered as a medical product in their country. Five respondents stated that this
substance was used in research or as analytical standards. There was no stated use for
animal/veterinary care
HARMFUL USE
Twenty-three respondents confirmed that there was recreational/harmful use of methylone
with 8 reporting oral/ inhaling/sniffing, 6 stating only oral, 2 stating oral/injection,
inhaling/sniffing and 1 stating inhaling/sniffing as common routes of administration.
Seventeen respondents stated this was obtained via trafficking and one each reporting
clandestine manufacturing, diversion plus trafficking and trafficking plus clandestine
manufacturing. Common formulations available were reported as powder by 8, powder and
tablet by 4, powder, tablet and liquid by 3, tablet only by 1 and liquid forms only by one. 4
respondents each stated that it was used only by the general population and only in clubs
while two respondents stated its use was both in clubs and among general population.
Two respondents report overdose deaths, two and 18 respectively for 2012. The latter is for all
cathinones. Emergency room visits are reported as two by one respondent and as about 20 by
another, for 2012. One death is reported for 2010, and 4 emergency room visits in 2013 by
one respondent. Five respondents reported withdrawal, tolerance and other adverse effects or
medical illnesses. Hyperthermia and dehydration are described as prominent features. Other
include several sympathomimetic features.
CONTROL
Of those with information on this substance, 29 reported that methylone was controlled under
legislation that was intended to regulate its availability - 25 under controlled substance act,
2 under medicines law and 2 under other laws. Only 4 respondents stated that there were
challenges with the implementation of this legislation. On illicit activities involving
methylone, two reported clandestine manufacture where the product itself was synthesized.
Four respondents reported processing into the consumer product, 16 reported trafficking, four
reported diversion and 15 an internet market.

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Details on seizures are presented below.

Total number of seizures

Total quantity seized (kg)
Total quantity seized (L)
Total quantity seized
(tablets/pills)
Others seized

2011
(number of respondents)
2,133 (14)
705.97 (12)
2,881 (5)

2012
(number of respondents)
4,428 (14)
229.74 (14)
1 (1)
56,430 (7)

Wraps/ pieces/ bags

Wraps/pieces/bags

IMPACT OF SCHEDULING
Twenty-nine respondents reported that if methylone was placed under international control,
they would have the laboratory capacity to identify the substance. It has no reported medical
use.

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