Mephedrone

Mephedrone (2-methylamino-1-p-tolylpropan-1-one), also known as 4-methylmethcathinone (4-MMC), or 4-methylephedrone, is a stimulant and entactogen drug of the amphetamine and cathinone chemical classes. It is reported to be contained in some legal highs and is sometimes sold mixed with methylone. It is a synthetic substance based on the cathinone compounds found in the khat plant of eastern Africa. Mephedrone can come in the form of capsules, tablets or white powder that users may swallow, snort or inject. In 2009 it became the fourth most popular street drug in the United Kingdom, behind marijuana, cocaine, and ecstasy.

Appearance
Mephedrone is a white substance. It is sold most commonly as crystals or a powder, but also in the form of capsules or pills.

Synthesis
Mephedrone can be synthesised by adding 4-methylpropiophenone dissolved in glacial acetic acid to bromine to create an oil fraction of 4'-methyl-2-bromopropiophenone. This is then dissolved in CH2Cl2 and drops of the solution are added to another solution of CH2Cl2 containing methylamine hydrochloride and triethylamine. Hydrochloric acid is then added and the aqueous layer is removed and turned alkaline using sodium hydroxide before the amine is extracted using CH2Cl2. The CH2Cl2 is then evaporated using a vacuum creating an oil which is then dissolved in a non-aqueous ether. HCl gas is then bubbled through the mixture to produce 4-methylmethcathinone hydrochloride.



History
The Psychonaut Research Project, an EU organisation that searches the internet for information regarding new drugs, first identified mephedrone in 2008. Their research suggests that the drug first became available in 2007. Mephedrone was first seized in France in May 2007 after police sent a tablet that they assumed to be ecstasy to be analysed. The drug was used in early products, such as Neodoves pills, by the legal high company Neorganics, but the range was discontinued in January 2008 after the government of Israel, where the company is based, made mephedrone illegal. It has been reported to be sold as a designer drug, but little is known about its pharmacology or toxicology at present. Mephedrone has recently been reported as having been sold as "ecstasy" in the Australian city of Cairns, along with ethylcathinone,  and has also been reported in Europe and the United States. It is reportedly currently manufactured in China. The Daily Telegraph reported that manufacturers are making "huge amounts of money" from selling the drug. In January 2010 Druglink magazine reported that dealers in Britain spend £2,500 to ship one kilogram from China but can sell it on for £10 a gram making a profit of £7,500. A later report, in March 2010, stated that the wholesale price of mephedrone was £4000 per kilogram.

Use in the United Kingdom
Between the summer of 2009 and March 2010 the use of mephedrone grew rapidly in the UK, becoming freely available at music festivals, head shops and on the internet. The drug is used by a diverse range of social groups including teenagers, polydrug using nightclubbers, psychonauts and over 40s with no previous experience of drug use. Whilst the evidence is anecdotal, researchers, charity workers, teachers and users have all reported widespread and increasing use of the drug. The reasons for the rapid growth in popularity is believed to be related to both the availability and legality of the drug. Criminologists also believe that the emergence of mephedrone is related to the decreasing purity of MDMA and cocaine on sale in the UK.

Intended effects
According to the company Crew2000, intended effects include increased alertness, euphoria, excitement, feeling of stimulation, urge to talk and openness. Psychologists at Liverpool John Moores University are conducting research into the effects of mephedrone on up to 50 students. Les Iversen, the chair of the Advisory Council on the Misuse of Drugs called the experiments "pretty unethical".

Side effects
According to the Darlington Drug and Alcohol Action Team, mephedrone can cause nose bleeds, nose burns, hallucinations, nausea, vomiting, blood circulation problems, rashes, anxiety, paranoia, fits, and delusions. According to Crew2000, other side effects may include poor concentration, poor short-term memory, increased heart rate, abnormal heart beats, anxiety, depression, increased sweating, dilated pupils, the inability to normally open the mouth, and teeth grinding.

A survey conducted by the National Addiction Centre, UK found that 51% of mephedrone users said they suffered from headaches, 43% from heart palpitations, 27% from nausea and 15% from cold or blue fingers.

Long-term effects
BBC News reported that one person who used the drug for 18 months, in the end using it twice a week, had to be admitted to a psychiatric unit after he started experiencing hallucinations, agitation, excitability and mania. Almost nothing is known about the long term effects of the drug due to the short history of its use.

Typical use and consumption
The Guardian reported that some users compulsively redose, consuming their whole supply when they only meant to use a small dose. A survey conducted in late 2009 by the National Addiction Centre (UK) found that one in three readers of Mixmag had used mephedrone in the last month, making it the fourth most popular drug amongst clubbers.

Harm reduction
The charity Lifeline recommends that to reduce the potential harm caused by using mephedrone, users should only use mephedrone occasionally (less than weekly), use less than 0.5g per session, dose orally rather than snort the drug and avoid mixing it with alcohol and other drugs.

Toxicity
At present, very little is known about the toxicity of 4-methylmethcathinone. In 2009, one case of sympathomimetic toxicity was reported in the UK after a person took 0.2 g of mephedrone orally and 3.8 g subcutaneously. They were treated with 1 mg of lorazepam and the sympathomimetic features decreased within 6 hours of treatment. Reported side effects suggest it may cause pronounced peripheral vasoconstriction, which has been speculated to result from formation of the potent vasoconstrictor 4-methylephedrine as a metabolite, a compound known to have significantly more cardiovascular toxicity than ephedrine itself. The Swedish medical journal, Läkartidningen reported that mephedrone could theoretically cause the cardiovascular problems associated with the use of cocaine and amphetamines and serotonin syndrome associated with the use of ecstasy and LSD. Reports of addiction and problematic use have also emerged. Professor David Nutt, former chair of the Advisory Council on the Misuse of Drugs (ACMD) in the UK has said "people are better off taking ecstasy or amphetamines than those [drugs] we know nothing about" and "Who knows what's in [mephedrone] when you buy it? We don't have a testing system. It could be very dangerous, we just don't know. These chemicals have never been put into animals, let alone humans." Les King, a former member of the ACMD, has stated that it appears to be less potent than amphetamine and ecstasy but that any benefit associated with this could be negated by users taking larger amounts. He also told the BBC "all we can say is [mephedrone] is probably as harmful as ecstasy and amphetamines and wait until we have some better scientific evidence to support that."

Deaths
In 2008, an 18 year-old Swedish woman died in Stockholm after taking mephedrone allegedly in combination with cannabis. An ambulance was soon called to Bandhagen after the girl went into convulsions and turned blue in the face, Svenska Dagbladet reported. Doctors reported that she was suffering from hyponatremia and an autopsy revealed the woman's brain had swollen. Mephedrone was scheduled to be classified as a "dangerous substance" in Sweden even before the girl's death at Karolinska University Hospital on Sunday, 14 December, but the death brought more media attention to the drug. The possession of mephedrone became classified as a criminal offence in Sweden on 15 December 2008.

The death of a teenager in the UK in November 2009 was widely reported as being caused by mephedrone but a report by the coroner concluded that she died from natural causes. According to criminologists, the reporting of the death by newspapers followed "the usual cycle of ‘exaggeration, distortion, inaccuracy and sensationalism" associated with the reporting of recreational drug use.

There have been other unconfirmed reports speculating about the role mephedrone has played in the deaths of several young people in the UK. Cathinones have been implicated in the deaths of 18 people in England and 7 in Scotland but there is currently no conclusive scientific proof that mephedrone has been responsible for any deaths in the UK.

Legal status

 * Australia: Mephedrone is not specifically listed as prohibited in Australia. Federal Police have stated that it is an analog to methcathinone and therefore illegal. In February 2010, 22 men were arrested in conjunction with importing mephedrone. In March 2010 a youth was convicted of importing the drug and sentenced to six months alternate detention.
 * Canada: According to The Globe and Mail, mephedrone is considered a controlled substance by Health Canada.
 * Croatia: Mephedrone became illegal in Croatia on January 4, 2010.
 * Denmark: Denmark's Minister for Health and Prevention, Jakob Axel Nielsen, banned mephedrone, flephedrone and ethylcathinone on December 18, 2008. This is from the Ministry of Health and Disease Prevention press release.
 * Estonia: Classified as a "narcotic or psychotropic" substance and added to controlled substances list on November 27, 2009.
 * Finland: Through the Medicines Act, 4-methylmethcathinone is classified as a "medicinal product", making it illegal to manufacture, import, possess, sell, or transfer without a prescription. (from ot.fi, date unknown and City.fi, September 5, 2008)
 * Germany: Mephedrone became illegal in Germany on January 22, 2010.
 * Guernsey: It is illegal to import mephedrone into Guernsey.
 * Hungary: As of February 2010, mephedrone is legal in Hungary but legislators are considering whether to make it illegal.
 * Republic of Ireland: Mephedrone is currently legal but possession and supply of the drug will become illegal in June 2010.
 * Isle of Man:The Medicines Act 2003 was changed in February 2010 in the Isle of Man so that the import and sale of mephedrone is now illegal.
 * Israel: In December 2007, 4-methylmethcathinone was added to Israel's list of controlled substances, making it illegal to buy, sell, or possess.
 * Jersey: Classified as a Class C drug in 2009.
 * Netherlands: In March, 2010, the Dutch Ministry of Health and the Medicines Authority IGZ informed the Ministry of Justice that they now consider Mephedrone an unregulated medicine and sales and distribution of it are now prohibited.
 * New Zealand: Classified as a Class C drug under the Misuse of Drugs Act 1975.
 * Norway: The "Derivatbestemmelsen" is an Analog Act-type law in Norway that controls 4-methylmethcathinone, Bk-MBDB, Bromo-DragonFLY, 1,4-butanediol, GBL, and MBDB. See legemiddelverket.no. (last updated April 29, 2009)
 * Poland: Mephedrone is still legal in Poland (27.02.2010), but it can be mistakenly regarded as amphetamine by police since it comes out as amphetamine in standard police tests.
 * Romania On February 10, 2010 Romania revised its drug policy including 4-mmc and all cathinone related products to Table I considering it a high risk narcotic. Possession, sale, manufacture or distribution are punishable by 10 to 20 years in prison.
 * Singapore As of February 2010 mephedrone is legal in Singapore, 'CNN Go' reported that it is ordered over the internet and exported from the UK.
 * Sweden: Classified as a "health hazard" or "hazardous substance" ("hälsofarlig vara") pending further legislation, a ban on 4-methylmethcathinone went into effect on December 15, 2008, making its sale illegal. On June 15, 2009 it was classified as a narcotic.
 * United Kingdom: On March 29, 2010, Home Secretary Alan Johnson announced a ban of mephedrone and other synthetic "legal highs" would be enacted into law "within weeks" - a ban that will also seek to include other substituted cathinones.
 * United States: 4-Methylmethcathinone is unscheduled in the United States but has been made illegal in North Dakota. Those selling the drug for human consumption may however, be prosecuted under the Federal Analog Act due to its similarity to MDMA.