By David Nutt
On December 14th the government put into effect new controls against a whole range of synthetic cannabinoids.
This was their third round of controls against these new hyper-potent recreational cannabis agonist drugs that have taken over many of our prisons and also are wreaking havoc in the homeless population. The first two sets of controls on the earlier synthetic cannabinoids were rapidly surmounted by “underground” chemists who found new cannabis analogues to replace the banned ones. In an attempt to prevent this happening again the ACMD recommended to the Home Office that this third set of regulations should cover a more extensive range of substances. To achieve this they recommended banning a range of chemical series that were a part of the current crop of synthetic cannabinoids and which they predicted would necessarily be part of any future synthetic cannabinoid drugs. Any drug meeting these chemical criteria is now controlled as a Class B Schedule 1 drug under the Misuse of Drugs Act 1971.
When DrugSciences's chemistry experts heard of this plan early in 2016 they pointed out to the ACMD that this was a misguided approach. The chemical structures they were proposing to ban were contained in a number of current medicines such as the anti-inflammatory medicine indomethacin and in several of the sartan anti-hypertensive agents. These would therefore become illegal once the new law was enacted. The ACMD didn’t respond to our suggestions but presumably took the criticism on board as, when the regulations were announced, they tried to get around the problem by specifically exempting medicines that would otherwise have become illegal. The list given in the new regulation covers the following medicines - clonitazene, etonitazene, acemetacin, atorvastatin, bazedoxifene, indometacin, losartan, olmesartan, proglumetacin, telmisartan, viminol, zafirlukast.
However this exemption-based approach has a fatal flaw. Most, if not all, of these drugs were derived from chemical series that contain precursors to other drugs that might also be developed as medicines. Because these investigatory and precursor chemicals are not in the public domain they cannot be exempted, so are by default illegal. The new law means they would fall into Schedule 1 and Class B of the MDAct1971, making anyone caught supplying them liable to up to 14 years in prison and simple possession up to 5 years. These threats to researchers will have a chilling, possibly fatal, impact on pharmaceutical drug discovery research in the UK since complying with the regulations around Schedule 1 Class B drugs adds a vast cost burden to industry and academic researchers. As DrugScience has pointed out, experience with similar legislation over cathinones and ketamine analogues tells us that research on this type of compound effectively stops dead once whole chemical series are outlawed [1,2,3].
What is remarkable is that the Home Office appears to have ignored not only DrugScience, but also its own regulations on consultation before enacting the new amendment. The body representing the pharmaceutical industry – the ABPI – [the Association of the British Pharmaceutical Industries] was apparently not consulted and is now up in arms about the new law. Neither it appears were the UK universities, some of whom have medical or pharmaceutical chemistry research groups. One academic research chemist has told me that it is now likely that in almost all organic chemistry practical classes at some point a now-illegal substance will be made!
Moreover this approach is very unlikely to impact the availability of synthetic cannabinoids since they are so potent that they are almost impossible to detect and easily smuggled into prisons [they can easily be hidden absorbed into small tabs of paper]. Worse there is very limited evidence – if any – that the first two synthetic cannabinoid bans led to a reduction in usage or sales. The ACMD may now have created the worst possible outcome, an ineffective new law that could produce severe collateral damage to the UK research community.
What should the Home Office do in addition to retracting the new law? First they should stop the behaviour that led to the synthetic cannabinoid problem in the first place: the enhanced policing and testing of the public and prisoners for herbal cannabis. Second they should work with a range of experts to develop ways to identify and test the pharmacology of specific synthetic cannabinoids so that specific drugs, and not general chemical classes, are made illegal – this is the approach used by the UN and WHO. I suspect one reason they don’t want to use this evidence-based approach is because their current Schedule 1 status makes research with these compounds so difficult and costly that few (if any) groups have the resources and resolve to conduct such research. If legislative control is thought politically necessary, then a more rational approach would be to regulate new synthetic cannabinoids under the Psychoactive Substances Act, which at least has the benefit of exempting researchers from possession penalties.
Also they should develop other solutions to the harms done by synthetic cannabinoids particularly by resurrecting antagonists to these drugs that will reverse the toxic actions of these in the same way that naloxone reverses the dangerous effects of heroin. Last year I put a paper explaining this approach to the all-party parliamentary interest group on drugs and drug addiction but it seems there is no government route to support this kind of intervention. Perhaps the ACMD could take up this challenge and so do something useful for the field?
- Nutt DJ, King LA, Nichols DE (2013) Effects of Schedule I drug laws on neuroscience research and treatment innovation. Nat Rev Neurosci. Aug;14(8):577-85. doi: 10.1038/nrn3530. Epub 2013 Jun 12
- Nutt DJ (2011) Perverse effects of the precautionary principle: how banning mephedrone has unexpected implications for pharmaceutical discovery Advances in Psychopharmacology 1: 35-36 DOI 10.1177/2045125311406958
- Nutt, D. J., King, L. A., & Nichols, D. E. (2013). New victims of current drug laws. Nat Rev Neurosci. doi:1038/nrn3530-c2 Ref 467