Mephedrone

Mephedrone, also known as 4-methylmethcathinone (4-MMC), or 4-methylephedrone, is a synthetic stimulant and entactogen drug of the amphetamine and cathinone 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. Slang names include meph, drone and MCAT. In late 2009, UK newspapers began referring to the drug as meow or miaow (sometimes doubled as meow meow or miaow miaow), a name that was almost unknown on the street at the time.

History
According to the EMCDDA, the synthesis of mephedrone was first reported in 1929 by Saem de Burnaga Sanchez, under the name "toluyl-alpha-monomethylaminoethylcetone", but the compound remained an obscure product of academia until 2003, when it was "re-discovered" and publicised by an underground chemist from The Hive working under the pseudonym "Kinetic." 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. Whilst the evidence is anecdotal, researchers, charity workers, teachers and users have all reported widespread and increasing use of the drug. The drug's rapid growth in popularity is believed to be related to both its availability and legality. Criminologists also believe that the emergence of mephedrone is related to the decreasing purity of ecstasy and cocaine on sale in the UK, with average cocaine purity falling to 22% in 2009 (from 60% in 1999) and about half of ecstasy pills seized in 2009 containing no MDMA. Media organisations including the BBC and The Guardian incorrectly reported that mephedrone was commonly used as a plant fertiliser. In fact sellers of the drug describe it as "plant food" as it is illegal to sell the compound for human consumption.

On 30 March 2010, Alan Johnson announced that mephedrone would be made illegal "within weeks" after the Advisory Council on the Misuse of Drugs (ACMD) sent him a report on the use of cathinones. Prior to the ban being announced, Dr Polly Taylor, a member of the ACMD resigned, saying she "did not have trust" in the way the government would use the advice given by the ACMD. Eric Carlin, another member of the ACMD, also resigned after the announcement that mephedrone would be made illegal, saying that the decision by the Home Secretary was "unduly based on media and political pressure". He stated that there was "little or no discussion about how our recommendation to classify this drug would be likely to impact on young people's behaviour."

Some ex-members of the ACMD, and various charity groups have expressed concern regarding the banning of the drug, arguing it will inevitably criminalise users, particularly young people. Others have expressed concern that the drug will now be left in the hands of irresponsible dealers, who will only compound the problem. The ACMD has very publicly run into problems with the UK Government recently regarding drug policy, many of these problems fuelled by the decision to prohibit Mephedrone and other related cathinones. Eric Carlin's resignation was specifically linked to the criminalisation of mephedrone, and he stated: "We need to review our entire approach to drugs, dumping the idea that legally-sanctioned punishments for drug users should constitute a main part of the armoury in helping to solve our country’s drug problems. We need to stop harming people who need help and support". Consequently, the mephedrone debate has led to a general questioning of UK drugs policy.

Intended effects
According to the company Crew2000, intended effects of mephedrone include increased alertness, euphoria, excitement, feeling of stimulation, and openness. Psychologists at Liverpool John Moores University are conducting research into the effects of mephedrone on up to 50 students already using the drug. 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 (gurning). 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. Doctors at Guy's Hospital, London reported that of 15 patients they treated after taking mephedrone, 53.3% were agitated, 40% tachycardic, 20% had systolic hypertension and 20% had seizures. 20% were treated with benzodiazepines, predominantly to control their agitation. They reported that none of their patients suffered from cold or blue peripheries, as other reports have done.

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. However, there is no evidence supporting a causal link. Almost nothing is known about the long-term effects of the drug due to the short history of its use. Because of its similarity to cathinone, John Mann, professor of chemistry at Queen's University Belfast, has posited that mephedrone is likely to cause impotence with long-term use.

Typical use and consumption
The Guardian reported that some users compulsively redose, consuming their whole supply when they are 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. An Irish study of people on a methadone treatment program for heroin addicts found that 29 out of 209 patients tested positive for mephedrone usage.

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. Users should also drink plenty of water whilst taking the drug as it causes dehydration.

Pharmacology
Writing in the British Medical Journal, psychiatrists stated that given its chemical structure, "mephedrone is likely to stimulate the release of, and then inhibit, the reuptake of monoamine neurotransmitters".

Toxicity
At present, nothing is known about the potential neuro-toxicity of mephedrone. 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."

Sweden
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 comatose and suffering from hyponatremia and severe hypokalemia; an autopsy after her death on the second hospital day revealed cerebral edema. 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.

UK
There have been unconfirmed reports speculating about the role mephedrone has played in the deaths of several young people in the UK. By April 2010, cathinones had been implicated in the deaths of 18 people in England, 7 in Scotland, 1 in Wales and 1 in Northern Ireland. As of June 2010, mephedrone use has been established as a cause of death in only one case in England, that of 46 year old, Stirling Smith, who had underlying health problems and repeatedly injected the drug. 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. Toxicology reports following the deaths of two teenagers (Louis Wainwright, 18, and Nicholas Smith, 19) that were widely reported by the media to be caused by mephedrone, and which led to a ban on the substance in April 2010, showed that the teenagers had in fact not taken any mephedrone. According to Fiona Measham, a criminologist who is a member of the ACMD, 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.

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. It has a distinct strong odour.

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.



Legal status

 * Australia: Mephedrone is not specifically listed as prohibited in Australia. Federal Police have stated that it is an analogue 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.
 * Belgium: Mephedrone became illegal in Belgium on Jun 13, 2010.
 * Canada: According to The Globe and Mail, mephedrone is considered a controlled substance by Health Canada. According to the Canadian Medical Association, mephedrone is grouped with other amphetamines as Schedule III controlled substances.
 * 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.
 * Europe: The European Monitoring Centre for Drugs and Drug Addiction are reviewing the situation and will report their findings in July 2010.
 * 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)
 * France: Mephedrone became illegal in France on Jun 11, 2010.
 * 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 illegal since May 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 to include 4-mmc and all cathinone-related products in Table I, considering it a hig-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: Quickly 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 and taken very seriously by the courts, with 15 grams and above resulting in a minimum of two years in prison - meaning gram for gram it gives heavier sentences than cocaine or heroin
 * United Kingdom: On 7 April 2010 the Misuse of Drugs Act 1971 (Amendment) Order 2010 was passed by parliament, making mephedrone and other substituted cathinones Class B drugs from 16 April 2010.  Prior to the ban taking effect, mephedrone was not covered by the Misuse of Drugs Act 1971. It was however an offence under the Medicines Act to sell it for human consumption, so it was often sold as "plant food" or "bath salts" although, as it has no use as such products, this too was possibly illegal under the Trade Descriptions Act 1968.   The importation of mephedrone was banned on 29 March 2010.
 * 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 Methcathinone.