the known unknowns of mephedrone

The current debate in the UK about mephedrone is generating a lot of heat but not so much light.  Perhaps a look at the underlying science might point out some issues that have not been widely discussed. Let’s start at the end of 2009 when several “legal high” drugs were banned.

One of these was Spice, sold in head shops and on the internet and marketed as a herbal smoking mixture that promised a natural high.  Spice was very popular as a cannabis substitute and did indeed offer a high to those who smoked it.  It took some time before it was realised that Spice was not an innocuous herbal mixture.  It turned out that someone, probably in the Far East, was concocting a herbal mixture and then spraying this with some chemicals that had been shown to mimic the action of tetrahydrocannabinol (THC), the active principal of cannabis.  Two of the more popular chemicals used were JWH-018, originally synthesised in an academic lab in the US as part of a curiosity driven research programme and CP 47,497 originally synthesised by Pfizer as a potential drug but not developed.  Both of these compounds had been shown by their originators to mimic potently the actions of THC.  Other THC-mimics were also found in some batches of Spice and eventually the JWH-018 chemical itself became available over the internet. 

What do we learn from this?  Spice was not a uniform product and those who smoked it were consuming an unknown mixture of psychoactive chemicals.  Although the levels of these chemicals were not high, the levels were not defined, and neither was their purity.  Many of the chemicals had not been properly tested for toxic effects such as neurotoxicity or causing cancer or birth defects.  When JWH-018 became available it was also of uncertain purity and it’s availability meant that people could consume larger amounts leading to some frightening effects.  So the lessons from the Spice story are that people smoking Spice mixtures or taking JWH-018 were taking big risks as they didn’t know the composition or purity of the material and the potential toxic effects were undefined.

Let’s now move to 2010 and the recent controversy over mephedrone.  Mephedrone is a member of a class of chemicals called cathinones and has been available through head shops and the internet.  Cathinone was originally identified as the active compound in Khat, a plant preparation chewed as a stimulant  in Africa and the Arabian peninsula.  Mephedrone itself is not found in khat but is a synthetic cathinone.

We have a rudimentary idea about how some of the cathinones work; they have been shown to alter the brain levels of chemical messengers called neurotransmitters in a similar but not identical way to amphetamine or ecstasy.  The psychological effects of mephedrone reported by users are consistent with this.  Mephedrone has, however, been synthesised only recently and as a result there is no firm information on how it works or how it might affect brain function when consumed on a longer term basis.  We also have no idea about its potential toxic effects (neurotoxicity, cancer, birth defects etc).  As with JWH-018 there is the issue of the purity.  The suppliers of mephedrone on the internet claim high purity but there is no guarantee that the figures are accurate and samples obtained elsewhere may be cut with undefined substances.    

So in both the cases I have described, people are consuming chemicals of uncertain purity, unknown toxicity and, in the case of mephedrone, unknown biology.    We would not tolerate this situation in a pharmaceutical drug.  Indeed the unregulated situation with mephedrone is reminiscent of the mid 20th century era of pharmaceuticals.   I am also reminded of the story that emerged in 1982 when heroin addicts in California were sold a synthetic narcotic contaminated with an impurity called MPTP.   MPTP turned out to be a neurotoxin causing a syndrome very like Parkinson’s disease in users. 

Both Spice and mephedrone have now been banned but I doubt if this will contain the situation.  Demand for these kinds of drugs is not going to go away, and this will be satisfied by the internet and by synthesis of new compounds.  Chemical synthesis in the Far East is available readily and cheaply and there are reports that more chemicals have been prepared in time for the banning of mephedrone.  The ingenuity of these suppliers will ensure other chemicals enter our market.

What can be done?   The government should urgently set up a research programme on the biological and toxic effects of these new substances.  We would then know how the substances work and whether they do or do not pose risks.  We also need to understand why people want to take these drugs.  We could then use this knowledge about the drugs to educate people about the risks they may be running in taking them.




One thought on “the known unknowns of mephedrone”

  1. Whilst the situation you describe with mephedrone can’t be faulted, I don’t think it really highlights anything new (as you actually allude to with respect to MPTP) since purity and composition are perpetual bedfellows with the illicit/unregulated drug market; there are similarities between the JWH situation and doctoring of Chinese herbal medicines used for hypersensitivity disorders than were spiked with corticosteroids.

    The really interesting thing that your piece highlights for me is the trend within the modern world to focus on purity and efficacy and that this legitimate focus within the clinical sphere could drive the emphasis on the same factors in the illicit drug industry.

    Ironically, I highlight this in mahy of the cannabis lectures I give since there are lots of examples of psychoactive substances that have demonstrated increased risk in modern times as a nof increased purity/potency. Example would be cannabis (herb vs oil; THC psychosis), opiates (opium resin vs heroin; dependency, respiratory depression etc), hallucinogens (Amanita, nutmeg etc vs LSD; psychotic episodes), cocaine (leaves vs crack).

    I suppose this does beg the question: if khat were available instead of mephedrone, would the same problems have occurred?

    That’s not to advocate legalisation of low potency narcotics (!), just some thoughts to suggest that there may be other factors involved that we – as the scientists, researchers, clinicians etc – have a duty to consider.

    Great piece – a really interesting read.


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