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Mephedrone , also known as 4- methyl methcathinone 4-MMC or 4- methyl ephedrone , is a synthetic stimulant drug of the amphetamine and cathinone classes. In addition to its stimulant effects, mephedrone produces side effects , of which bruxism is the most common. The metabolism of mephedrone has been studied in rats and humans and the metabolites can be detected in urine after usage. Mephedrone was first synthesised in , but did not become widely known until it was rediscovered in at which point it was legal to produce and possess in many countries. By , mephedrone was reported to be available for sale on the internet, by law enforcement agencies had become aware of the compound, and by , it had been reported in most of Europe, becoming particularly prevalent in the United Kingdom. Mephedrone was first made illegal in Israel in , followed by Sweden later that year. In , it was made illegal in many European countries and in December , the EU ruled it illegal. Users have reported that mephedrone causes euphoria , stimulation , an enhanced appreciation for music , an elevated mood , decreased hostility , improved mental function and mild sexual stimulation ; these effects are similar to the effects of cocaine, amphetamines and MDMA, and last different amounts of time depending on the way the drug is taken. Of 70 Dutch users of mephedrone, 58 described it as an overall pleasant experience and 12 described it as an unpleasant experience. The users were also asked to compare the 'risk', and they answered that it was equal. This was contrary to another study in New Zealand, where users of benzylpiperazine thought that because it was legal, it was safe. Mephedrone can come in the form of capsules, tablets or white powder that users may swallow, snort, inject, smoke or use rectally. The effects last for between two and three hours when taken orally or nasally, but only half an hour if taken intravenously. One published study that analysed samples of mephedrone bought using the internet in the UK in found it was racemic a mixture of both stereoisomers and of high purity. Other effects users in internet forums have noted include changes in body temperature, increased heart rate , breathing difficulties , loss of appetite, increased sweating , discolouration of extremities, anxiety , paranoia and depression. They reported none of their patients suffered from cold or blue peripheries, contrary to other reports. Nine of the 15 of patients had a Glasgow coma scale GCS of 15, indicating they were in a normal mental state, four had a GCS below 8, but these patients all reported using a central nervous system depressant, most commonly GHB , with mephedrone. The patients also reported polydrug use of a variety of compounds. Neurotoxic effect of mephedrone on serotonin 5-HT and dopamine DA systems remains controversial. Although some studies in animal models reported no damage to DA nerve endings in the striatum and no significant changes in brain monoamine levels, some others suggested a rapid reduction in 5-HT and DA transporter function. Persistent serotonergic deficits were observed after binge like treatment in a warm environment and in both serotonergic and dopaminergic nerve endings at high ambient temperature. Oxidative stress cytotoxicity and an increase in frontal cortex lipid peroxidation were also reported. There have been reports of users craving mephedrone, suggesting it may be addictive. In , one case of sympathomimetic toxicity was reported in the UK after a person took 0. Shortly afterwards, the user 'developed palpitations, blurred tunnel vision, chest pressure and sweating'. He was treated with lorazepam and discharged 15 hours after admission. Simon Gibbons and Mire Zloh of the School of Pharmacy, University of London stated, based on the chemical similarities between methcathinone and mephedrone, 'it is highly likely that mephedrone will display neurotoxicity'. They concluded more experimental research is needed to investigate the toxicity of mephedrone. Doctors who treated a year-old female suffering from mephedrone intoxication suggested in The Lancet that, like MDMA, mephedrone may promote serotonin-mediated release of antidiuretic hormone , resulting in hyponatraemia and an altered mental state. The doctors treating the patient stated it was caused by either a direct toxic effect of mephedrone on the heart muscle, or by an immune response. The patient started to recover after arriving at the hospital and it was not necessary to administer any medication. In , an year-old Swedish woman died in Stockholm after taking mephedrone. The newspaper Svenska Dagbladet reported the woman went into convulsions and turned blue in the face. An autopsy showed severe brain swelling. The possession of mephedrone became classified as a criminal offence in Sweden on 15 December In , unconfirmed reports speculated about the role mephedrone has played in the deaths of several young people in the UK. By July , mephedrone had been alleged to be involved in 52 fatalities in the UK, but detected in only 38 of these cases. Of the nine that coroners had finished investigating, two were caused directly by mephedrone. Toxicology reports showed the teenagers had not taken any mephedrone and had died as a result of consuming alcohol and the heroin substitute methadone. Mephedrone has been implicated in the death of a year-old male, who had also injected black tar heroin. Mephedrone was found in his blood at a concentration of 0. The blood concentration of morphine, a metabolite of heroin, was 0. Mephedrone is a monoamine releasing agent. It is a chiral compound and both of its enantiomers display similar potency as substrates at dopamine transporters. R -Mephedrone is much less potent than S -mephedrone as a substrate at serotonin transporters. The keto oxygen renders mephedrone more hydrophilic than the corresponding methylamphetamines , which may account for the higher doses required to achieve a similar effect, because mephedrone is less able to cross the blood—brain barrier. Mephedrone is often consumed with alcohol. A study in mice investigated the interrelation between these two substances, focusing on the psychostimulant and rewarding properties of mephedrone. It found that at low non stimulant doses alcohol significantly enhanced the psychostimulant effects of mephedrone. This effect was mediated by an increase in synaptic dopamine , as haloperidol , but not ketanserin , was able to block the potentiation by alcohol. Similarly, the rewarding properties of mephedrone were enhanced by a low non-rewarding dose of alcohol. Several articles published near the end of examined the effects of mephedrone, compared to the similar drugs MDMA and amphetamine in the nucleus accumbens of rats, as well as examining the reinforcing potential of mephedrone. Dopamine and serotonin were collected using microdialysis, and increases in dopamine and serotonin were measured using HPLC. Reward and drug seeking are linked to increases in dopamine concentrations in the nucleus accumbens, and drug half-life plays a role in drug seeking, as well. They reached their peak concentrations at 40 minutes and 20 minutes, respectively, and returned to baseline by minutes after injection. Analysis of the ratio of the AUC for dopamine DA and serotonin 5-HT indicated mephedrone was preferentially a serotonin releaser, with a ratio of 1. Additionally, half-lives for the decrease in DA and 5-HT were calculated for each drug. Mephedrone had decay rates of MDMA had decay values of Taken together, these findings show mephedrone induces a massive increase in both DA and 5-HT, combined with rapid clearance. The rapid rise and subsequent fall of DA levels could explain some of the addictive properties mephedrone displays in some users. Based on the analysis of rat and human urine by gas chromatography and mass spectrometry , mephedrone is thought to be metabolised by three phase 1 pathways. It can be demethylated to the primary amine producing compounds 2, 3 and 5 , the ketone group can be reduced producing 3 or the tolyl group can be oxidised producing 6. Both 5 and 6 are thought to be further metabolised by conjugation to the glucuronide and sulfate derivatives. Knowledge of the primary routes of metabolism should allow the intake of mephedrone to be confirmed by drug tests , as well as more accurate determination of the causes of side effects and potential for toxicity. Mephedrone may be quantitated in blood, plasma or urine by gas chromatography-mass spectrometry or liquid chromatography-mass spectrometry to confirm a diagnosis of poisoning in hospitalised patients or to provide evidence in a medicolegal death investigation. Mephedrone is a white substance. It is sold most commonly as crystals or a powder, but also in the form of capsules or pills. Mephedrone can be synthesised in several ways. The simplest method, due to the availability of the compounds, \\\\\\\\\\\\\[4\\\\\\\\\\\\\]: The oil fraction can then be dissolved in dichloromethane CH 2 Cl 2 and drops of the solution added to another solution of CH 2 Cl 2 -containing methylamine hydrochloride and triethylamine. Hydrochloric acid HCl is then added and the aqueous layer is removed and turned alkaline using sodium hydroxide before the amine is extracted using CH 2 Cl 2. The CH 2 Cl 2 is then evaporated using a vacuum, creating an oil which is then dissolved in a nonaqueous ether. Finally, HCl gas is bubbled through the mixture to produce 4-methylmethcathinone hydrochloride. It can also be produced by oxidising the ephedrine analogue 4-methylephedrine using potassium permanganate dissolved in sulfuric acid. Because 4-methylephedrine can be obtained in a specific enantiomeric form, mephedrone consisting of only one enantiomer can be produced. The danger associated with this method is it may cause manganese poisoning if the product is not correctly purified. Mephedrone does not react with most reagent testing kits. The exception is the Liebermann reagent , which gives a bright yellow reaction. Mephedrone is one of hundreds of designer drugs or legal highs that have been reported in recent years, including artificial chemicals such as synthetic cannabis and semisynthetic substances such as methylhexanamine. These drugs are primarily developed to avoid being controlled by laws against illegal drugs, thus giving them the label of designer drugs. A drug similar to mephedrone, containing cathinone , was sold legally in Israel from around , under the name hagigat. When this was made illegal, the cathinone was modified and the new products were sold by the Israeli company, Neorganics. Their research suggested the drug first became available to purchase on the internet in , when it was also discussed on internet forums. Europol noted they became aware of it in , after it was found in Denmark, Finland and the UK. Between the summer of and March , the use of mephedrone grew rapidly in the UK, with it becoming readily available at music festivals , head shops and on the internet. Whilst the evidence was anecdotal, researchers, charity workers, teachers and users reported widespread and increasing use of the drug in Fiona Measham, a criminologist at The University of Lancaster , thought the emergence of mephedrone was also related to the decreasing purity of ecstasy and cocaine on sale in the UK, \\\\\\\\\\\\\[35\\\\\\\\\\\\\] a view reinforced in a report by the National Treatment Agency for Substance Misuse. In comparison, over a similar time period, the entries for cocaine and MDMA were accessed approximately times. Media organisations including the BBC and The Guardian incorrectly reported mephedrone was commonly used as a plant fertiliser. In fact sellers of the drug described it as 'plant food' because it was illegal to sell the compound for human consumption. The police report was used as a source for the story in The Sun. On 30 March , Alan Johnson , the then Home Secretary , announced mephedrone would be made illegal 'within weeks' after the ACMD sent him a report on the use of cathinones. We need to stop harming people who need help and support'. The parliamentary debate was held on 8 April, one day after the general election had been announced, meaning it was during the so-called ' wash-up period ' when legislation is passed with little scrutiny. Only one hour was spent debating the ban and all three parties agreed, meaning no vote was required. Compared to previous surveys, more users purchased it from dealers, rather than the internet. Of the various drugs used by the survey participants, users were more likely to have concerns about it. Rather than the price rising due to increased scarcity of the drug, it is thought to have risen for two other reasons. Firstly, dealers knew there was still demand for mephedrone, but were aware the supplies may be exhausted in the future. Secondly, the dealers perceived customers were likely to be willing to pay more for an illegal substance. Professor Shiela Bird, a statistician at the Medical Research Council , suggested the ban of mephedrone may lead to more cocaine-related deaths. In the first six months of , the number of cocaine-related deaths fell for the first time in four years, and fewer soldiers tested positive for cocaine in than in She suggested this may have been due to users switching to mephedrone from cocaine, but cautioned that before full figures are available for and , it will be difficult to determine whether mephedrone saved lives, rather than cost them. Cases of intravenous use were also reported to be on the increase. When mephedrone was rediscovered in , it was not specifically illegal to possess in any country. As its use has increased, many countries have passed legislation making its possession, sale and manufacture illegal. It was first made illegal in Israel , where it had been found in products such as Neodoves pills, in January In , as its use became more prevalent, many countries passed legislation prohibiting mephedrone. On 7 April , the Misuse of Drugs Act Amendment Order was passed by parliament, making mephedrone and other substituted cathinones , Class B drugs from 16 April In some countries, mephedrone is not specifically listed as illegal, but is controlled under legislation that makes compounds illegal if they are analogs of drugs already listed. In Australia during , it was not specifically listed as prohibited, \\\\\\\\\\\\\[48\\\\\\\\\\\\\] but the Australian Federal Police stated it is an analogue to methcathinone and therefore illegal. It is now listed as a Schedule 9 prohibited substance in Australia under the Poisons Standard October In New Zealand , it is not included in the Misuse of Drugs Act , \\\\\\\\\\\\\[\\\\\\\\\\\\\] but is illegal, as it is similar to controlled substances. In Canada , mephedrone is not explicitly listed in any schedule of the Controlled Drugs and Substances Act , but 'amphetamines, their salts, derivatives, isomers and analogues and salts of derivatives, isomers and analogues' are included in Section 19 of Schedule I of the act. Cathinone and methcathinone are listed in separate sections of Schedule III, while diethylpropion and pyrovalerone also cathinones , are listed in separate sections of Schedule IV, each without language to capture analogues, isomers, etc. The Drug Enforcement Administration DEA states, as an analogue of methcathinone , possession of mephedrone can be controlled by the Federal Analog Act , but according to the Los Angeles Times , this only applies if it is sold for human consumption. Except as authorised by law, this action made possessing and selling mephedrone or the products that contain it illegal in the US for at least one year while the DEA and the United States Department of Health and Human Services conduct further study. Of those, two thirds snorted the drug and the average dosage per session was 0. Users who snorted the drug reported using more per session than those who took it orally 0. These chemicals have never been put into animals, let alone humans. 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. From Wikipedia, the free encyclopedia. Not to be confused with methedrine , methedrone , methadone , methylone , methcathinone , or ephedrone. Anlage I Authorized scientific use only UK: This section needs to be updated. Please update this article to reflect recent events or newly available information. Bath salts 4-Methylamphetamine 4-Methylbuphedrone 4-Methylcathinone 4-Methylpentedrone 4-Methylthioamphetamine Methamphetamine para -Methoxyamphetamine. Ecstasy and Related Drug Trends Bulletin. Archived from the original PDF on 17 February Annales de Toxicologie Analytique. Progress in Neurology and Psychiatry. Advisory Council on the Misuse of Drugs. Archived from the original on 10 February Perceptions of safety and sources of supply'. International Journal of Drug Policy. The Drug Treatment Centre Board. Journal of Medical Toxicology. British Medical Journal Case Reports. Annual Report ' PDF. Archived from the original PDF on 2 January Drugs and Alcohol Today. Journal of Analytical Toxicology. British Journal of Pharmacology. Journal of Pharmacology and Experimental Therapeutics. Analytical and Bioanalytical Chemistry. Analysis of synthetic cathinones commonly found in bath salts in human performance and postmortem toxicology: Annales de Toxicologie Analytique in French. Archived from the original PDF on 10 February Inside the nation saying yes to drugs'. Retrieved 22 March Psychonaut Web Mapping Project. The Drug Enforcement Administration. Archived from the original PDF on 17 October Retrieved 29 January State Food and Drug Administration, P. Archived from the original on 15 August Should miaow-miaow be banned? International Narcotics Control Board. Archived from the original PDF on 2 April Retrieved 26 March Annex 1 to the Risk assessment report: Technical report on mephedrone PDF Report. National Treatment Agency for Substance Misuse. Truth or trumped-up charges? Way back in January , not long after mephedrone first began to be sold online, members of the web forum attached to the now-defunct ' headshop ' Champagne Legals discussed what brand name they might attach to the new product, which has the chemical identity dimethylmethcathinone or MM-Cat. The name did not catch on But on 1 November , someone did add the name 'Meow' to the Wikipedia entry for Mephedrone at the head of a list of 'street names. Archived from the original on 31 January Transform Drug Policy Foundation. Retrieved 13 April How banning mephedrone has unexpected implications for pharmaceutical discovery'. Therapeutic Advances in Psychopharmacology. Independent Scientific Committee on Drugs. BBC Radio 5 Live. Regulation amending the Ordinance Archived from the original PDF on 15 July Retrieved 14 September Archived from the original on 21 September Retrieved 17 March Croatian Ministry of Health and Social Welfare. Selected laws in Germany — Buzer. The Health Ministry has established a list of plants and other substances with psychoactive properties that will be banned, after it has been proven that they are dangerous to health\\\\\\\\\\\\\] in Romanian. Isle of Man Today. Archived from the original on 28 February Retrieved 4 July Description of the control measures that are applicable to mephedrone in the Member States'. Office of Public Sector Information. Irish Department of Health and Children. Archived from the original on 21 February Retrieved 22 August Archived from the original on 15 February Belgian Department of Justice. Italian Ministry of Health. Archived from the original on 27 June Retrieved 2 January Archived from the original on 4 April French Ministry of Health and Sports. Archived from the original on 26 October Постановление от 29 июля г. Retrieved 1 September United Nations Office on Drugs and Crime. New Zealand Ministry of Health. Canadian Department of Justice. Canadian Medical Association Journal. Archived from the original on 22 August United States Drug Enforcement Administration. New York State Health Department. The Irish Medical Journal. Calea zacatechichi Silene capensis. Coffee break Coffeehouse Latte art Tea house. Abuse Date rape drug Impaired driving Drug harmfulness Effects of cannabis Addiction Dependence Prevention Opioid replacement therapy Rehabilitation Responsible use Drug-related crime Fetal alcohol spectrum disorder Long-term effects of cannabis Neurotoxicity Overdose Passive smoking of tobacco or other substances. Alcohol legality Alcohol consumption Anabolic steroid legality Cannabis legality Annual use Lifetime use Cigarette consumption Cocaine legality Cocaine use Methamphetamine legality Opiates use Psilocybin mushrooms legality Salvia legality. Adapromine Amantadine Bromantane Memantine Rimantadine. Oxiracetam Phenylpiracetam Phenylpiracetam hydrazide. SoRI Adrenergic release blockers: Retrieved from ' https: Drugs not assigned an ATC code Cathinones Euphoriants Phenethylamines Sympathomimetics Designer drugs Vasoconstrictors Serotonin-norepinephrine-dopamine releasing agents Substituted amphetamines Entactogens and empathogens. Views Read Edit View history. In other projects Wikimedia Commons. This page was last edited on 4 October , at By using this site, you agree to the Terms of Use and Privacy Policy. Oral , insufflation , IV , rectal , \\\\\\\\\\\\\[1\\\\\\\\\\\\\] smoking \\\\\\\\\\\\\[2\\\\\\\\\\\\\].

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