Article

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

School of Pharmacy, College Lane Campus, University of Hertfordshire, Hatfield, Herftordshire, AL10 9AB, UK.
Psychopharmacology (Impact Factor: 3.88). 11/2010; 214(3):593-602. DOI: 10.1007/s00213-010-2070-x
Source: PubMed

ABSTRACT

Recently, 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.
We 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.
Because 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.
Within 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.

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    • "NPS are also called " legal highs " because due to their easily and therefore rapidly changing chemical structure they are difficult to control. For example, mephedrone, a stimulant with an effect similar to cocaine and amphetamine, was legal before 2011 and cheaper than other drugs (Schifano et al., 2011), which may explain its rapid spread on the drug market. MDPV, which was legal in Hungary until 2012, causes acute neurological, cardiovascular and psychotic symptoms such as tachycardia, hypertension, hypothermia, and hallucination (Coppola and Mondola, 2012; Szily and Bitter, 2013). "
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    ABSTRACT: Background: There has been an almost exponential growth in the number of new psychoactive substances (NPS) on the drug markets in Europe during the past decade. While most users of NPS use them by routes other than injecting, percutaneous use of NPS is associated with very frequent injecting episodes and paraphernalia sharing. Methods: We assessed to what extent new clients between 2006 and 2014 (N=3680) at Blue Point, Hungary's largest needle exchange program, exhibited a shift during these years in the drugs they primarily injected. Results: Until 2010, 99% of clients injected either heroin or amphetamines. After 2010, however, there was a "replacement chain" of new substances, with one appearing and disappearing after the other: between 2010 and 2014, NPS under five names appeared and gained dominant prevalence (from 0% to 80%), and gradually replaced first the two "traditional" drugs amphetamine and heroin (which diminished to 17% together in 2014) and later each other. We also saw an increase in the proportion of female and older clients. Conclusions: While our findings are restricted to injected NPS, they suggest that NPS affect the vast majority of the population of people who inject drugs not only in terms of drug use patterns, but maybe also in terms of demographics. Given that over 80% of people who inject drugs use NPS and injecting NPS is associated with increased injecting risks, harm reduction services should be made more available to avoid an epidemic of blood-borne infections.
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    • "However, after regulatory measures that restrict possession, sale, and manufacture of synthetic cathinones passed in the UK, the number of users who purchased the drug from dealers increased considerably, while its price increased, almost two times higher than its price before legislation [4]. Sometimes mephedrone is sold as either cocaine or ecstasy while cut-agents such as paracetamol, caffeine, amphetamine, ketamine and even cocaine may be found in mephedrone [1] [7]. As reported by users and drug-orientated websites, mephedrone is commonly used recreationally either via oral ingestion or insufflation. "
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    ABSTRACT: The aim of this work is to test the stability of mephedrone added to whole blood collected from alive and dead mephedrone free-users and stored at three different temperatures (-20, +4 and +20°C) with and without preservatives up to 6 months, trying to establish the best storage condition in order to reduce possible analyte loss/degradation during the storage period. Different sources of blood were obtained as follow: 10 samples of blood came from 10 alive mephedrone free-users (mean age 34±15.8 years old) (Group 1), whereas 10 post mortem blood samples were obtained from 10 cadavers, in which the post mortem interval was between 24 and 36h (Group 2). The cause of death in post mortem cases (mean age 45±14.2 years old) was not drug related. Pools of blood were spiked with mephedrone at the concentration of 1mg/L and 1mL aliquots were transferred in 2mL Eppendorf capped tubes with and without preservatives as follow: with ethylenediaminetetraacetic acid (EDTA) 3%; with sodium fluoride/potassium oxalate (NaF/KOx) 1.67%/0.2%, respectively; without preservatives. All samples were stored at three different temperatures: -20°C, 4°C and 20°C and extracted and analyzed in duplicate by GC-MS according to a previously published method by Dickson et al., every other day during the first month and then weekly up to 6 months. our study allow us to affirm that -20°C is the best storage temperature for mephedrone stability in ante-mortem and post-mortem blood samples in comparison to the other two tested temperatures (+4 and +20°C), showing higher values in both groups in samples stored with and without preservatives (p<0.0001). The comparison of Group 1 (samples coming from alive subjects) and Group 2 (post-mortem samples) highlights a better stability of mephedrone in Group 1 (p<0.001) at all tested storage conditions. Finally, the analysis of blood specimens stored with and without preservatives in both groups suggests that specimens stored with NaF/KOx maintain mephedrone stability better than those stored with EDTA (p<0.001) and those stored without preservatives (p<0.0001), therefore, we strongly recommend in order to maintain the highest mephedrone stability in blood, to store specimens at -20°C adding NaF/KOx as preservative. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.
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    • "administration to freely moving rats elevates extracellular levels of dopamine, and to a greater extent 5-HT, in the nucleus accumbens (Kehr et al. 2011; Baumann et al. 2012; Wright et al. 2012). Multiple re-dosing is common with mephedrone users attempting to maintain the desired effects of this shortacting drug, and while a typical recreational dose is often between 100–200 mg, individuals may re-dose and ingest up to 4 g in a single session (Schifano et al. 2011; Winstock et al. 2011). Most studies show the acute effect of a single injection, or self-administration of mephedrone in the rat is hypothermia (Aarde et al. 2013; Miller et al. 2013; Shortall et al. 2013a), but hyperthermia has also been reported following rapid repeated dosing (Hadlock et al. 2011; Baumann et al. 2012). "
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    ABSTRACT: The psychoactive effects of mephedrone are commonly compared with those of 3,4-methylenedioxymethamphetamine, but because of a shorter duration of action, users often employ repeated administration to maintain its psychoactive effects. This study examined the effects of repeated mephedrone administration on locomotor activity, body temperature and striatal dopamine and 5-hydroxytryptamine (5-HT) levels and the role of dopaminergic and serotonergic neurons in these responses. Adult male Lister hooded rats received three injections of vehicle (1 ml/kg, i.p.) or mephedrone HCl (10 mg/kg) at 2 h intervals for radiotelemetry (temperature and activity) or microdialysis (dopamine and 5-HT) measurements. Intracerebroventricular pre-treatment (21 to 28 days earlier) with 5,7-dihydroxytryptamine (150 µg) or 6-hydroxydopamine (300 µg) was used to examine the impact of 5-HT or dopamine depletion on mephedrone-induced changes in temperature and activity. A final study examined the influence of i.p. pre-treatment (-30 min) with the 5-HT1A receptor antagonist WAY-100635 (0.5 mg/kg), 5-HT1B receptor antagonist GR 127935 (3 mg/kg) or the 5-HT7 receptor antagonist SB-258719 (10 mg/kg) on mephedrone-induced changes in locomotor activity and rectal temperature. Mephedrone caused rapid-onset hyperactivity, hypothermia (attenuated on repeat dosing) and increased striatal dopamine and 5-HT release following each injection. Mephedrone-induced hyperactivity was attenuated by 5-HT depletion and 5-HT1B receptor antagonism, whereas the hypothermia was completely abolished by 5-HT depletion and lessened by 5-HT1A receptor antagonism. These findings suggest that stimulation of central 5-HT release and/or inhibition of 5-HT reuptake play a pivotal role in both the hyperlocomotor and hypothermic effects of mephedrone, which are mediated in part via 5-HT1B and 5-HT1A receptors. © 2015 Society for the Study of Addiction.
    No preview · Article · Jul 2015 · Addiction Biology
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