People have been using psychoactive drugs for pleasure for thousands of years. From the Areca nut used as a mild stimulant in Timor over 13,000 years ago, to the coca leave cultivated in South America 5,000 years ago it seems the human brain craves stimulation, and consequently, new and interesting stimulants. Modern day humans are no exception. We're all used to hearing news stories about heroin, cocaine, ecstasy and LSD, but lately there has been an explosion in both the number and types of new drugs available.
WHAT'S THE PROBLEM?
Regulatory authorities are struggling to keep up with the number of new "illegal" drugs on the market. I say "illegal" simply because it's not clear how these compounds should be classified. The complexity in the law governing the use of drugs arises from the subtleties of the chemistry at the atom level. For instance, for any given compound, legal or not, a difference of a single atom anywhere in the structure results in a compound which is completely unique. There may not be anything known about this novel compound, and consequently, there is no legislation governing it's use.
For example, lets examine the chemical composition of two drugs, one legal decongestant called pseudoephedrine, and one illegal drug called methamphetamine, (crystal meth). Pseudoephedrine is available from pharmacies as an over the counter medication. It's the active ingredient in Sudafed for example. Structurally, pseudoephedrine looks very similar to methamphetamine, see the picture below. In fact there are just two atoms in the difference.
If nothing was known about pseudoephedrine a toxicologist looking at it for the first time might expect it to have a similar effect to methamphetamine, that is, stimulatory, promoting alertness, and increasing reaction time. But it's very difficult to judge the effect of those two extra atoms. The additional (-OH) present on pseudoephedrine could make it more or less potent as a stimulant. Perhaps it's metabolised more quickly by the body? Perhaps it's more soluble in the blood now? Perhaps it has a harder time getting into the brain? A good toxicologist can make good predictions, but they are just that. Until detailed studies are performed it's really not known how a particular drug will behave.
This is the root of the difficultly for legislators. If there was a decision to make pseudoephedrine illegal this might go some way to curbing it's use. However, a single atom change to it's structure results in an entirely new compound. It's perfectly possible that nothing is known about the physiological effects of this compound, beyond it's ability to produce a chemical high. This is exactly what happened with ecstasy (MDMA) production recently. One of the precursor ingredients for MDMA was made illegal. The idea was to make it more difficult to manufacture MDMA and ultimately make people safer.
However, far from making people safer this change in legislation resulted in the rise of a new ecstasy like compound called PMMA. Both MDMA and PMMA have similar effects, but the effects of PMMA come on much more slowly. Thinking the drugs weren't working, or that they had taken a really low dose, regular MDMA users would take more and more PMMA waiting for the effects to kick in. Needless to say, when the effects did kick in things got serious. Very quickly after the emergence of PMMA there were media reports of overdoses across Ireland and the UK. Sadly, this is a stark example of legislation that was introduced to prevent harm actually causing more harm than good.
This is the root of the difficultly for legislators. If there was a decision to make pseudoephedrine illegal this might go some way to curbing it's use. However, a single atom change to it's structure results in an entirely new compound. It's perfectly possible that nothing is known about the physiological effects of this compound, beyond it's ability to produce a chemical high. This is exactly what happened with ecstasy (MDMA) production recently. One of the precursor ingredients for MDMA was made illegal. The idea was to make it more difficult to manufacture MDMA and ultimately make people safer.
However, far from making people safer this change in legislation resulted in the rise of a new ecstasy like compound called PMMA. Both MDMA and PMMA have similar effects, but the effects of PMMA come on much more slowly. Thinking the drugs weren't working, or that they had taken a really low dose, regular MDMA users would take more and more PMMA waiting for the effects to kick in. Needless to say, when the effects did kick in things got serious. Very quickly after the emergence of PMMA there were media reports of overdoses across Ireland and the UK. Sadly, this is a stark example of legislation that was introduced to prevent harm actually causing more harm than good.
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| Fuck it, lets just make everything legal! |
MEDIA ATTENTION ON DRUGS
2014 saw the introduction of over 100 new synthetic drugs of abuse in Europe alone. With such a wide array of new street drugs it's no longer surprising to encounter a news story including the name of a drugs most of us have never heard before. For example, this was a recent headline in America.
The drug being referred to here is called alpha-pyrrolidinopentiophenone, or alpha-PVP for short, street name Flakka, or Gravel. But what is this drug, and where did it come from?
ALPHA-PVP
Alph-PVP is a synthetic stimulant which belongs to a class of drugs called cathinones. Cathinone itself is naturally occurring, being found in the plant called Khat. The leaves of this plant can be chewed to produce mild stimulation. The structure of cathinone is shown below, along with the khat plant it's found in. Interestingly you can see it looks a little bit like methamphetamine, so it's not too surprising to learn that this drug is a stimulant. It also induces paranoid delusions, with users reportedly fearing for their lives after hallucinating gangs of people chasing them down!
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| The chemical structure of cathinone (left) and the plant which makes it Catha edulis, (right). |
At this point it's important to point out here that whether or not a compound is synthetic has no bearing on its safety or toxicity. There are many synthetic compounds which are safe, and many natural compounds that are dangerous. In the case of PVP, the naturally occurring cathinone molecule was modified by a chemist to produce a novel synthetic compound. This is the case with all synthetic cathinones which include mephedrone (M-CAT, Meow, Meow), and MDPV, (Bath Salts), both of which get sporadic media attention as a result of fatal or near fatal overdoses. The structures of these compounds are shown below. If you know a little chemistry you can see they look a little like the structure of cathinone, shown above. Variants of cathinone are continously made to circumvent the laws which ban them. Thus, it is often not illegal to manufacture or sell these compounds.
You could argue that all that's required for legislators to get a handle on this is an outright ban of all cathinone compounds. The problem with that idea is that some cathinones are actually medicinal, and are used as antidepressants for example. Making all cathinones illegal immediately makes research into these drugs more difficult. Any research laboratory wanting to investigate these compounds would now need to apply for a licence to have them on the premises. This is a bureaucratic nightmare, enough to put off many research scientists who simply don't have the knowledge or the resources to work in such a regulated environment. Regardless of whether or not you think this is a poor attitude for a scientist to take, the reality is more barriers to research means less research is done.
Those using synthetic cathinones recreationally can be often experience far more intense "highs" than expected. Part of the problem with illegal or unregulated drug manufacture is that the contents are not tightly controlled, so the potency between batches is extremely variable. By contrast, any drug manufactured legally by a pharmaceutical company must undergo a multitude of quality control (QC) checks to ensure purity before being distributed.
SUMMARY
SUMMARY
New drugs are being manufactured all the time. Legislation designed to protect the population from the risks and harms of drug use have actually compounded the problem resulting in deaths from the distribution of PMMA marketed as Ecstasy (MDMA). At the same time, there is increase in the number of synthetic cathinones, producing powerful psychoactive stimulants. Almost nothing is known about the physiological effects and safety of these stimulants. By contrast, the physiological effects of compounds such as amphetamine, methamphetamine and cathinone itself, are known and documented in detail. I hope this segment has given some insight into the science behind the news headlines, and the difficulties faced by regulators and scientists working in this area.
As always, comments are welcome.
As always, comments are welcome.
USEFUL INFORMATION
- Database on new psychoactive drugs in Europe
- Guardian Science Podcast on PMMA
- FOX news article on Alpha-PVP
- Information on Synthetic Cathinones.
- Irish Times News Story on PMMA Deaths
- Review of Flakka
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