What should be done about mephedrone?

BMJ 2010; 340 doi: http://dx.doi.org/10.1136/bmj.c1605 (Published 24 March 2010) Cite this as: BMJ 2010;340:c1605

This article has a correction. Please see:

  1. Adam R Winstock, senior lecturer in addiction psychiatry 1,
  2. John Marsden, reader in addiction psychology1,
  3. Luke Mitcheson, consultant clinical psychologist2
  1. 1Institute of Psychiatry, King’s College London, London SE5 8AF
  2. 2South London and Maudsley NHS Trust, London SE5 8AZ
  1. adam.winstock{at}kcl.ac.uk

    We should focus on crafting the most effective public health response

    The recent deaths of two young men who are thought to have taken the β keto-amphetamine stimulant mephedrone (4-methylmethcathinone) have prompted urgent calls for the drug to be banned. As we write, there is no certainty that mephedrone caused these two deaths, but it may be implicated. Amphetamine-type stimulants are known to cause about 100, mostly accidental, deaths a year in the United Kingdom.1 Stimulant related deaths typically result from a sympathomimetic toxidrome—a constellation of symptoms and signs that can be seen with excessive consumption of stimulant type drugs—accompanied by cardiac conduction problems, cerebral haemorrhage, and sometimes hyperpyrexia. Other drugs and alcohol are commonly used at the same time,1 and may have been in the latest cases. Most drug related deaths (about 1100 cases a year in the UK) involve one or more central nervous system depressants—including opioids, alcohol, and sedatives—at doses that cause respiratory depression.2

    Almost unheard of two years ago, mephedrone—colloquially known as “Miaow,” “4-MMC,” “Meph,” and “TopCat”—has grown quickly in popularity and is now widely available for purchase online. So called “legal highs” have been available for decades, but recently web based marketing has facilitated their profitable sale. It is hard to determine the risks of mephedrone with any accuracy because its toxicity and metabolism are still largely unknown, unlike other stimulant drugs such as cocaine and ecstasy (3,4 methylenedioxymethamphetamine).

    Mephedrone is a synthetic stimulant that is chemically related to cathinone, the psychoactive chemical class present in the khat plant.3 It is usually sold as a white crystalline or off-white-yellow powder (as a hydrochloride salt) for about £10 (€11; $15) per gram. Consumption is usually oral or intranasal and rarely by injection. Sellers avoid attracting the attention of regulatory bodies by labelling the substance “not for human consumption,”4 which means that no advice on safer use and dosing is provided.

    Given its chemical structure, mephedrone is likely to stimulate the release of, and then inhibit, the reuptake of monoamine neurotransmitters. Its perceived effects are dose related and include euphoria, increased energy, feelings of empathy, increased libido, sweating, tachycardia, headache, and teeth grinding.5 Users may exhibit features of excitement, hyperactivity, talkativeness, and dilated pupils although the precise presentation will vary depending on dose, tolerance, and the consumption of other substances. On online forums, users report experiencing rashes, cold blue fingers and toes (perhaps related to peripheral vasoconstriction), and, in the days after use, typical stimulant comedown symptoms such as lethargy and low mood.6

    Currently, mephedrone seems to be the most popular of the synthesised cathinone stimulants, although several others are available, including methylone (4-methylenedioxy-N-methylcathinone) and butylone (3,4-benzodioxolylbutanamine), both of which have unknown health risks. It seems to be most popular among young clubbers (18-25 years), but is also used by a wider population of older adolescents and young adults.7 Recently surveyed mephedrone users reported that the drug gives a better quality high than cocaine.8 Some researchers have suggested that mephedrone’s popularity reflects, in part, dissatisfaction with the purity and consistency of available cocaine and ecstasy among regular stimulant users,7 who now seek out mephedrone instead. But concern also exists that mephedrone may be taken by young people with little previous experience of drug use.

    Reports of patients who have presented to hospital after taking mephedrone describe an expected cluster of cardiovascular signs, with agitation and sometimes a brief drug induced psychosis.9 People with underlying cardiac, neurological, and psychiatric conditions, especially those on medication, are likely to be at greatest risk of serious adverse events. Mephedrone is highly likely to be used along with other stimulant drugs or alcohol that moderate or enhance its effects, and this may contribute to an increased risk of adverse effects. A drug induced increase in libido may lead to risky sexual behaviour.

    Credible educational and harm reduction advice about this drug are urgently needed. However, mephedrone is an unknown quantity in terms of harms, risks, and dose related effects; we know nothing of its potential neurotoxicity or the long term consequences of its use. As such, all that may be offered is the same commonsense advice that might be given about the use of any psychoactive stimulant. Advice should include avoiding regular use to avoid developing tolerance; not using the drug in combination with other stimulants or large amounts of alcohol and other depressants; not injecting the drug; remaining well hydrated when using the drug; and avoiding becoming overheated. Use is likely to be particularly hazardous in people with a history of mental health disorders, cardiac problems, or neurological disorders, and in those currently on medication for these conditions. Chronic use is likely to lead to increased tolerance and addiction. A brief motivational intervention similar to those used for clients with alcohol or other drug dependence might reasonably be delivered by a healthcare worker, and specialist psychosocial interventions could be adapted to treat mephedrone addiction if necessary.

    Both the Advisory Council on the Misuse of Drugs and the European Monitoring Centre on Drugs and Drug Addiction are gathering evidence on risks and harms associated with mephedrone. In all likelihood the UK government will move to control the manufacture, distribution, and possession of this drug, and possibly that of similar compounds, which would see a sharp fall in online sales. However, the drug would probably still find its way to users not deterred from purchasing drugs via the illicit market. It is hard to judge whether controlling mephedrone under the current provisions of the Misuse of Drugs Act is the best public health response. Recent history suggests that manufacturers will merely turn their attention to the nearest effective but unsanctioned alternative substance. Unfortunately, the list of potential synthetic psychoactive compounds is dauntingly long.


    Cite this as: BMJ 2010;340:c1605


    • Competing interests: All authors have completed the Unified Competing Interest form at www.icmje.org/coi_disclosure.pdf (available on request from the corresponding author) and declare: (1) No financial support for the submitted work from anyone other than their employer; (2) No financial relationships with commercial entities that might have an interest in the submitted work; (3) No spouses, partners, or children with relationships with commercial entities that might have an interest in the submitted work; (4) No non-financial interests that may be relevant to the submitted work.

    • Provenance and peer review: Commissioned not externally peer reviewed.


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