Il-Legal Highs: Telling the difference

25 April 2013

Interview with

Dr. John Ramsey, St. George's University of London

Hannah - Last year in the UK, 73 completely new legal high drug compounds were found in clubs and bought over the internet by the police.  But how do scientists keep up with this constant flow of new and untested chemicals that are being released and flooding the market? 

Chris - Analytical Toxicologist John Ramsey explained to me how his company, TICTAC Communications which produce a commercial drug database used by UK Healthcare and law and order professionals, track the appearance of new drugs, and what constitutes a legal high.

John R. - A legal high is a compound not controlled by Misuse of Drugs Act. Drugs that mimic existing drugs of misuse but are being modified sufficiently to just tweak them to bring them outside the Misuse of Drugs Act, but similar enough to maintain the pharmacology. Of course at the time they're synthesized and sold, nobody really knows whether they do that or not, but the assumption is that the molecular adjustments are relatively minor. Therefore, they will retain the pharmacology. Then they get marketed and evaluated by the users who report back whether they work or not and then they're either successful if they work as drugs or they're not successful, I guess, if they don't.

Chris - So, how do you stay on top of this?

John R. - It's a completely moving goalpost. We discover a new compound, we find out about it, we tell the legislators, they make it illegal, and then the bad guys look for a new compound. So, we go round and round this circle with a constant number of new compounds being made and detected, and then controlled.

Chris - So, do you have to dip into the marketplace - for want of a better word - to see what's doing the rounds then to keep updated?

John R. - Yes, we have lots of different strategies. I mean, we can only work within the law obviously, that's one issue. So, we use the contents of club amnesty bins to see what's being used in the great outdoors as it were.

Chris - Club amnesty bin?

John R. - Clubs are known to have a drug problem, so they need to do the best they can to minimise drug use on their premises. So, they will agree with the local police and the local licensing authority on a strategy to keep drugs out. And what it normally says is, they reserve the right to search people as a condition of entry to the club and if they find anything during the course of that search, as long as it's deemed to be small enough for people for personal use, as long as it's surrendered then people are allowed to go in the club, and the club operates normally.

Chris - And they dump the stuff into the bin and you're then able to access what they've dumped.

John R. - The police effectively collect the drugs from the amnesty bins and then they're brought to us by various police forces, then we analyse them chemically and then put them in our database.

Chris - How do you analyse a tablet you find in an amnesty bin?

John R. - The sort of routine methods. Essentially, infrared spectroscopy for powders because it's quick and cheap and then we follow that up with GC-MS, gas chromatography-mass spectrometry.  The gas chromatography separates the drugs into its various components and the mass spectrometry effectively produces a fingerprint which identifies them.

Chris - How do you know this is a drug which actually will produce an effect in a user? In other words, it is a substance that has the potential to be illegal.

John R. - Well usually, they're sufficiently similar to an existing drug. I mean, some of them are literally minor modifications of existing drugs.

Chris - What does it take for legislation to get changed about a chemical? So, you find a chemical which has come out of a club amnesty bin or customs send to you and say we're finding this on people, does just the sheer fact that you find a new molecule immediately mean it gets regulated or is there a process there?

John R. - There's a process, but the problem is that in 2012, there were 73 new compounds notified to the European monitoring centre. Most of those compounds will be controlled on a European basis, but before that happens, they're risk assessed. So, just the fact that a compound exists doesn't necessarily mean that it will be controlled.

Chris - Where are all these new molecules coming from? Are there people sitting in their garden sheds across the country cooking up this stuff or is it more organised than that?

John R. - It's much more organised than that. They're almost all manufactured in China and imported into this country in bulk and then distributed. But whether the  Chinese actually sit down and innovate the compounds and supply them or whether somebody in Europe or America commissions the synthesis, I think is unclear at the moment.

Chris - What about the fact that, yes, you could detect these things, you might find the one tablet in existence for that particular molecule, what about actually working out whether people are wholesale consuming an agent?  How can we do that?

John R. - That's a big problem. We can lurk around the chat rooms and hear what people are talking about, but that's not terribly scientific, but it gives us an idea as to whether they work or not. But we also have a strategy where we analyse bulk urine samples and look for the presence of these things. Typically, urine collections from public urinals and we take samples from those and we can analyse them as an anonymous pool bulk sample and find out what's in them on a Saturday night in a particular district.

Chris - I do remember reading a paper maybe about 10 years ago or so where someone had gone and collected samples from the River Po in Europe and said there must be something like a million doses of cocaine washing down the river everyday based on their findings. So, you can just go and analyse river water to find out what people are using. Can you sort of go to that extreme with these other molecules?

John R. - We absolutely can. I mean, the pooled urine analysis has more sensitivity.  You know, we're collecting undiluted urine from a couple hundred people typically.  When you get on to sewage treatment works, the number of drug uses contributing to the pool has to be quite high before we can detect it. Nonetheless, we can easily detect MDMA from ecstasy tablets, cocaine, heroin, methadone, and whole variety of other compounds as well. And indeed we have a project called SEWPROF which is researching exactly these issues. We're looking for differences in drug use in different countries and in different populations. We're looking for the effectiveness of strategies to try and defeat drug use. And we're also looking for the occurrence of these new compounds as they become available.

Chris - When I was a medical student, we were shown a video of the very famous case of the MPTP story. Someone was trying to make a heroin substitute and lots of people turned up with the symptoms of Parkinson's disease and that always stuck in my mind and I thought, if I was ever offered a tablet in a club, I would never take it because the person who made that drug did not know they put these other toxin in by accident. Are you quite worried by what you see cropping up in the chemicals that you've analysed?

John R. - Absolutely. I mean, the circumstances you describe were before the internet. I mean, goodness knows what would've happened if somebody had made that now. At the time, it was distributed to only about 15 or 16 people locally. But now, when the stuff is made, it's distributed to hundreds of thousands of people potentially across the whole of Europe or even across the whole of the world. So, there is the potential for an absolute catastrophe and I think young people just don't realise the potential risks they're running. They don't understand why the pharmaceutical industries spent hundreds of billions of dollars and 5 years risk assessing stuff before it ever gets near a human volunteer. This stuff is completely untested and probably the first person who takes it is somebody who buys it either off the internet or even from a high street shop.

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