**2. Recreational use**

Mephedrone (4-methylmethcathinone; 'Plant Food', 'Meow Meow', 'Miaow', 'Drone', 'Meph', 'Bubbles', 'Spice E', 'Charge', 'M-Cat', 'Rush', 'Ronzio', 'Fiskrens' and 'MMC Hammer') ( Schifano et al, 2011) is the most popular of the cathinone derivatives, which also include butylone, flephedrone, MDPV, methedrone, methylone, pentylone, and other compounds (ACMD, 2010; Morris, 2010). It has been readily available for purchase both online and in head shops as a 'legal high', and more recently as a 'research chemical'; its circulation has been promoted by aggressive web-based marketing (Deluca et al., 2009). Mephedrone elicits stimulant and empathogenic effects similar to amphetamine, methylamphetamine, cocaine and MDMA (Winstock et al., 2010). However, as we write, relatively few formal related papers and experimental/clinical data have been published (Dargan et al., 2010; Winstock et al., 2010; Winstock et al., 2011).

Mephedrone-Related Fatalities in the United Kingdom: Contextual, Clinical and Practical Issues 357

drug (Europol-EMCDDA, 2010). The risk assessment report, which was submitted to the European Commission and the Council of the European Union on 26 May 2010, examined the health and social risks of the drug, as well as information on international trafficking and the involvement of organised crime. Furthermore, the report considers the potential implications for placing the drug under control in the EU. On the basis of this report — and on the initiative of the European Commission — on 2 December 2010, the Council decided

In the UK, where mephedrone had been attracting great attention from both the mass media and the Government, the Advisory Council on the Misuse of Drugs (ACMD) submitted a report to the Home Office on the cathinone derivatives, recommending their inclusion in the Misuse of Drugs Act 1971 as a Class B drug (ACMD, 2010). The Home Office announced on 30 March 2010 that this recommendation would be enforced from 16 April 2010 (Home

Mephedrone is a semi-synthetic compound belonging to the chemical class of cathinone derivatives (or substituted cathinones). Cathinone is a natural amphetamine-like alkaloid found in the fresh leaves and stems of the African shrub Khat (Catha edulis) (Kalix, 1992). The systematic name of mephedrone is 2-(methylamino)-1-(p-tolyl)propan-1-one(2S)-2- (methylamino)-1-(4-methylphenyl)propan-1-one, in accordance with the International Union of Pure and Applied Chemistry. The structure of mephedrone differs from cathinone by methylation of the amino group and the benzene ring present (Gustaffsson and Escher, 2009; Osorio-Olivares et al., 2003). The cathinones are beta-keto derivatives of phenethylamines, and hence analogues of amphetamines (Chemspider, 2010). Since they are mainly synthetic in origin, beta-keto amphetamines are also known as 'bk designer drugs'. It is relatively easy to produce mephedrone in nonprofessional laboratories via bromination of 4-methylpropiophenone followed by reaction with methylamine or by oxidation of 4-

Although mainly sold in powder and crystal forms, mephedrone may be commercially available in tablets and included within vegetable-based capsules. It has been reported that mephedrone is sometimes sold in some countries as either ecstasy or 'synthetic' cocaine (Deluca et al., 2009; Schifano et al., 2011). Furthermore, it may be found mixed with adulterants, such as caffeine, paracetamol and even cocaine, amphetamine and ketamine (Camilleri et al., 2010), as well as with other methcathinones (as revealed by information supplied to the National Programme on Substance Abuse Deaths by coroners

Given the affiliation of cathinone derivatives to beta-keto amphetamines, mephedrone would be expected to act as a Central Nervous System stimulant. In vitro studies on the effects of the cathinone derivatives methcathinone and methylone confirm that the main mechanism of action is very similar to that of amphetamine, being characterised by a predominant action on plasma membrane catecholamine transporters (Cozzi et al., 1999). The presence of the ring substituent on the phenethylamine core modifies the

that mephedrone is to be subject to control measures (EMCDDA, 2011).

methylephedrine (Archer, 2009; Europol-EMCDDA, 2010).

Office, 2010).

**4. Chemistry** 

– see below).

**5. Pharmacology** 

The synthesis of mephedrone was first described over 80 years ago (Saem de Burnaga Sanchez, 1929). However, the first Internet reference to it occurred reportedly in May 2003 (Power, 2009), but both its availability for purchase online (Camilleri et al., 2010; Roussel et al., 2009) and its related popularity only started in 2007 (Deluca et al., 2009). Data collected by the European Monitoring Centre for Drugs and Drug Addiction (EMCDDA) indicate that during the first quarter of 2010, there were detections in some 20 EU Member States, with most of them reporting small- to medium-sized seizures (Europol-EMCDDA, 2010). During the second quarter of 2009, the UK Forensic Science Service received submissions of three times as many samples of mephedrone for analysis than it had in the previous 12-month period (ACMD, 2010; Ghodse et al., 2010). Since mephedrone appeared comparatively recently on the market, it does not feature in most drug use household surveys, and it is uncertain how many people present with a history of mephedrone misuse. Most available data originate from self-reported surveys and small focus group research.

The main settings for mephedrone use appear to be nightclubs, parties and people's homes (Newcombe, 2009). A survey of readers of the dance magazine 'Mixmag' found that 41.7% of respondents had ever tried mephedrone and 33.2% had used it during the previous month (Winstock et al., 2011). Dargan et al. (2010) assessed both the prevalence and frequency of use of mephedrone by students in Tayside (Scotland) in February 2010. Some 20.3% reported previous use of mephedrone; 23.4% reported using only using mephedrone on one occasion previously and 4.4% reported daily use. A total of 48.8% of users had sourced mephedrone from street-level dealers and 10.7% from the Internet. Heightened awareness and interest in mephedrone was reflected by a rise in the number of both telephone inquiries and visits to both the TOXBASE and FRANK web sites (ACMD, 2010; James et al., 2010). The 2011 sweep of the British Crime Survey, which covers households in England and Wales, found that 4.4% of adults aged 16 to 24 years had used mephedrone in the last year, compared to only 0.6% of those aged 25 to 59 years (Smith & Flatley, 2011). The rate for the younger age-group is similar to that for cocaine. The majority of respondents who had taken mephedrone in the last year had also taken another drug. It is, therefore, likely that it is existing users of drugs that are taking mephedrone rather than new users drawn to drug taking.

The emergence of mephedrone on the UK recreational drug scene may be linked to decreasing purity in the UK of both MDMA (ecstasy) and cocaine (Mulchandani et al., 2010; Fleming, 2010; Measham et al., 2010; NTA, 2010). As a consequence, drug users may have switched to mephedrone, as it was seen as cheaper and more powerful than the currently available 'traditional' stimulants (Deluca et al., 2009). Its availability over the Internet and its status as a 'legal high' (and therefore presumed not to be harmful) may have boosted its appeal (Daly, 2010; Ramsey et al., 2010).

#### **3. Legal status**

Mephedrone is not scheduled under the 1971 United Nations Convention on Psychotropic Substances. In Australia, New Zealand, and the USA mephedrone is considered as an analogue of other illegal substances already and can be controlled by laws similar to the Federal Analog Act. In March 2010, the EMCDDA and Europol submitted a joint report on mephedrone to the Council of the European Union, the European Commission and the European Medicines Agency (EMA), presenting the case for a formal risk assessment of the drug (Europol-EMCDDA, 2010). The risk assessment report, which was submitted to the European Commission and the Council of the European Union on 26 May 2010, examined the health and social risks of the drug, as well as information on international trafficking and the involvement of organised crime. Furthermore, the report considers the potential implications for placing the drug under control in the EU. On the basis of this report — and on the initiative of the European Commission — on 2 December 2010, the Council decided that mephedrone is to be subject to control measures (EMCDDA, 2011).

In the UK, where mephedrone had been attracting great attention from both the mass media and the Government, the Advisory Council on the Misuse of Drugs (ACMD) submitted a report to the Home Office on the cathinone derivatives, recommending their inclusion in the Misuse of Drugs Act 1971 as a Class B drug (ACMD, 2010). The Home Office announced on 30 March 2010 that this recommendation would be enforced from 16 April 2010 (Home Office, 2010).
