Mephedrone (4-methylmethcathinone; ‘meow meow’): chemical, pharmacological and clinical issues

BackgroundRecently, those substances deriving from the active ingredient of the Khat plant, cathinone, have been rising in popularity. Indeed, 4-methylmethcathinone (mephedrone; ‘meow meow’ and others) has been seen by some as a cheaper alternative to other classified recreational drugs.AimsWe aimed here at providing a state-of-the-art review on mephedrone history and prevalence of misuse, chemistry, pharmacology, legal status, product market appearance, clinical/management and related fatalities.MethodsBecause of the limited evidence, some of the information here presented has been obtained from user reports/drug user-orientated web sites. The most common routes for mephedrone recreational use include insufflation and oral ingestion. It elicits stimulant and empathogenic effects similar to amphetamine, methylamphetamine, cocaine and MDMA. Due to its sympathomimetic actions, mephedrone may be associated with a number of both physical and psychopathological side effects. Recent preliminary analysis of recent UK data carried out in 48 related cases have provided positive results for the presence of mephedrone at postmortem.Discussion and ConclusionsWithin the UK, diffusion of mephedrone may have been associated with an unprecedented combination of a particularly aggressive online marketing policy and a decreasing availability/purity of both ecstasy and cocaine. Mephedrone has been recently classified in both the UK and in a number of other countries as a measure to control its availability. Following this, a few other research psychoactives have recently entered the online market as yet unregulated substances that may substitute for mephedrone. Only international collaborative efforts may be able to tackle the phenomenon of the regular offer of novel psychoactive drugs.

[1]  H. Sumnall,et al.  The confusing case of NRG-1 , 2010, BMJ : British Medical Journal.

[2]  Anneke Poortman,et al.  Instability of the ecstasy market and a new kid on the block: mephedrone , 2011, Journal of psychopharmacology.

[3]  Olivier Roussel,et al.  Article original La 4-méthyléphédrone sera-t-elle une « Ecstasy » du XXIème siècle ? Is 4-methylephedrone, an "Ecstasy" of the twenty first century? , 2009 .

[4]  M. Johnston,et al.  Chemical analysis of four capsules containing the controlled substance analogues 4-methylmethcathinone, 2-fluoromethamphetamine, alpha-phthalimidopropiophenone and N-ethylcathinone. , 2010, Forensic science international.

[5]  J. Ramsey,et al.  Buying 'legal' recreational drugs does not mean that you are not breaking the law. , 2010, QJM : monthly journal of the Association of Physicians.

[6]  Kelly Morris,et al.  UK places generic ban on mephedrone drug family , 2010, The Lancet.

[7]  Fabrizio Schifano,et al.  Mass‐information: mephedrone, myths, and the new generation of legal highs , 2010 .

[8]  F. Schifano,et al.  Overview of Amphetamine-Type Stimulant Mortality Data – UK, 1997–2007 , 2010, Neuropsychobiology.

[9]  Wing-Sze Lee,et al.  The application of capillary electrophoresis for enantiomeric separation of N,N-dimethylamphetamine and its related analogs: intelligence study on N,N-dimethylamphetamine samples in crystalline and tablet forms. , 2007, Forensic science international.

[10]  R P Archer,et al.  Fluoromethcathinone, a new substance of abuse. , 2009, Forensic science international.

[11]  A. Winstock,et al.  Mephedrone, new kid for the chop? , 2011, Addiction.

[12]  P. Dargan,et al.  Clinical pattern of toxicity associated with the novel synthetic cathinone mephedrone , 2010, Emergency Medicine Journal.

[13]  Simon D Brandt,et al.  Analyses of second-generation 'legal highs' in the UK: initial findings. , 2010, Drug testing and analysis.

[14]  J. Griffith,et al.  Bupropion: clinical assay for amphetamine-like abuse potential. , 1983, The Journal of clinical psychiatry.

[15]  P. Kalix Cathinone, a natural amphetamine. , 1992, Pharmacology & toxicology.

[16]  M. C. Rezende,et al.  A two-step method for the preparation of homochiral cathinones , 2003 .

[17]  Y. Bentur,et al.  Illicit cathinone (“Hagigat”) poisoning , 2008, Clinical toxicology.

[18]  B. Levine,et al.  Multiple-drug toxicity caused by the coadministration of 4-methylmethcathinone (mephedrone) and heroin. , 2010, Journal of analytical toxicology.

[19]  P. Dargan,et al.  Mephedrone use and associated adverse effects in school and college/university students before the UK legislation change. , 2010, QJM : monthly journal of the Association of Physicians.

[20]  John Marsden,et al.  What should be done about mephedrone? , 2010, BMJ : British Medical Journal.

[21]  B. Rockstroh,et al.  Use of khat and posttraumatic stress disorder as risk factors for psychotic symptoms: a study of Somali combatants. , 2009, Social science & medicine.

[22]  Mike Power Mephedrone: the future of drug dealing? , 2010 .

[23]  Olivier Roussel,et al.  La 4-méthyléphédrone sera-t-elle une "Ecstasy" du XXIème siècle ? , 2009 .

[24]  M. Zloh,et al.  An analysis of the 'legal high' mephedrone. , 2010, Bioorganic & medicinal chemistry letters.

[25]  C. Escher,et al.  [Mephedrone--Internet drug which seems to have come and stay. Fatal cases in Sweden have drawn attention to previously unknown substance]. , 2009, Lakartidningen.

[26]  Fiona Measham,et al.  Tweaking, bombing, dabbing and stockpiling: the emergence of mephedrone and the perversity of prohibition , 2010 .

[27]  P. Kalix Pharmacological properties of the stimulant khat. , 1990, Pharmacology & therapeutics.

[28]  Yasushige Mori,et al.  Determination of the metabolites of the new designer drugs bk-MBDB and bk-MDEA in human urine. , 2009, Forensic science international.

[29]  F. Schifano Cocaine misuse dependence , 1996 .

[30]  M. Gygi,et al.  Methcathinone: an initial study of its effects on monoaminergic systems. , 1996, The Journal of pharmacology and experimental therapeutics.

[31]  J. Deschamps,et al.  1-(4-Methylphenyl)-2-pyrrolidin-1-yl-pentan-1-one (Pyrovalerone) analogues: a promising class of monoamine uptake inhibitors. , 2006, Journal of medicinal chemistry.

[32]  A. Ruoho,et al.  Inhibition of plasma membrane monoamine transporters by beta-ketoamphetamines. , 1999, European journal of pharmacology.

[33]  Fabrizio Schifano,et al.  Drugs on the web; the Psychonaut 2002 EU project , 2006, Progress in Neuro-Psychopharmacology and Biological Psychiatry.

[34]  B. Rockstroh,et al.  Khat use as risk factor for psychotic disorders: A cross-sectional and case-control study in Somalia , 2005, BMC medicine.

[35]  P. Dargan,et al.  Management of cocaine-induced cardiac arrhythmias due to cardiac ion channel dysfunction , 2009, Clinical toxicology.

[36]  David W. Holt,et al.  Recreational Use of Mephedrone (4-Methylmethcathinone, 4-MMC) with Associated Sympathomimetic Toxicity , 2010, Journal of Medical Toxicology.

[37]  F. Nagai,et al.  The effects of non-medically used psychoactive drugs on monoamine neurotransmission in rat brain. , 2007, European journal of pharmacology.

[38]  Fabrizio Schifano,et al.  Internet pharmacies and online prescription drug sales: a cross-sectional study , 2005 .

[39]  刘召贵,et al.  Chromatography, Mass spectrometry , 2001, Nature Biotechnology.

[40]  F. Schifano,et al.  "Legal highs" on the net-Evaluation of UK-based Websites, products and product information. , 2011, Forensic science international.

[41]  J. Kelly,et al.  A review of the neuropharmacological properties of khat , 2008, Progress in Neuro-Psychopharmacology and Biological Psychiatry.

[42]  R. Spears,et al.  Clinical characteristics of mephedrone toxicity reported to the UK National Poisons Information Service , 2010, Emergency Medicine Journal.

[43]  Frank T Peters,et al.  Beta-keto amphetamines: studies on the metabolism of the designer drug mephedrone and toxicological detection of mephedrone, butylone, and methylone in urine using gas chromatography–mass spectrometry , 2010, Analytical and bioanalytical chemistry.

[44]  J. Ramsey,et al.  Legal highs and the challenges for policy makers , 2010 .

[45]  J. Ramsey,et al.  Purchasing 'legal highs' on the Internet--is there consistency in what you get? , 2010, QJM : monthly journal of the Association of Physicians.

[46]  A. Ruoho,et al.  Inhibition of plasma membrane monoamine transporters by β-ketoamphetamines , 1999 .