Designer drugs dodge the law

Use of 3-MMC evident in sewage

Every year tens of new substances appear on the market in Europe; substances that actually have stimulating, psychotropic or narcotic effects, but that do not yet fall under the Dutch Opium Act. The trade, use or possession of these substances is therefore not illegal. These ‘designer drugs’ are purposefully made and developed with the aim of mimicking the effects of illegal drugs. Recently, for example, 3-MMC has been in the news; this is a variant of 4-MMC (‘mephedrone’ or ‘miauw miauw’) which is prohibited in the Netherlands. What’s going on – and what does wastewater analysis teach us about such new drugs?

Opium Act

By ‘drugs’ we mean narcotic, psychotropic or stimulating agents. The Opium Act recognises two types of drugs: ‘List I’ substances (hard drugs) and ‘List II’ substances (soft drugs). The trade, use or possession of these drugs is prohibited. Drugs that do not appear on these lists therefore do not fall under the Opium Act.

Designer drugs

However, there are also substances that actually have a stimulating, psychotropic and/or narcotic effect, but are not yet on the Opium Act’s lists. The trade, use or possession of these substances is therefore not prohibited. And that is precisely what some producers (‘designers’) take advantage of. They look at the chemical structure of the forbidden substances that have a known narcotic or stimulating effect, and modify the structure with a couple of – usually simple – chemical operations. For example, they move a small part of the molecule, or replace it with another part. Or they add an extra chemical group to the molecule, like a chlorine, bromine or fluorine atom or a methyl group (-CH3). The basic structure of the substance (and, they hope, also the effect) thus remains intact, while the ‘new psychoactive substance’ (NPS) does not appear on the lists of the Opium Act, and is therefore, for the time being, not prohibited.

Based on popular drugs

The starting point for the synthesis of an NPS is frequently the basic molecular structure of known and popular drugs, such as amphetamine, fentanyl or tryptamine. Some new psychoactive substances are developed by the pharmaceutical industry in its search for new medicines, while others are developed by clandestine laboratories. Most of these are described by Alexander and Ann Shulgin in their two books: PiHKAL (on phenethylamines) and TiHKAL (on tryptamines), which give details for their production process: perfect manuals for a chemical factory.

European market

The European Monitoring Centre for Drugs and Drug Addiction (EMCCDDA) in Lisbon keeps track of the number of designer drugs that appear on the European market, based on information from users, the online market, and law enforcement and healthcare systems. The figures below, taken from the EMCDDA 2020 annual report, show that tens of new, unique substances appear on the market every year, and that the total number of NPSs on the European market currently exceeds 400. The EMCDDA defines an NPS as: ‘a new narcotic or psychotropic drug, in pure form or in preparation, that is not controlled by the United Nations drug conventions, but which may pose a public health threat comparable to that posed by substances listed in these conventions’.

Opium Act modifications in the works

Regulatory bodies inevitably lag behind in imposing a possible prohibition on an NPS. The moment a new substance is forbidden, the designer can synthesize another one that is a lot like it. In some countries, the legislation is such that an NPS whose structure is derived from, or is very similar to, that of a prohibited substance, is itself also prohibited. In other countries, including the Netherlands, this is not the case. The Dutch government is however drafting legislation that includes substance groups on the Opium Act’s List I, whereby all substances derived from these substances’ basic structure are also automatically prohibited. The new Opium Act is only expected to enter into force in 2022.

Miauw miauw

4-MMC and 3-MMC provide a good example of how the legislation in the Netherlands currently works. 4-MMC, also known as ‘mephedrone’ or ‘miauw miauw’, is prohibited in the Netherlands and is included in List I of the Opium Act. The structure is very similar to methamphetamine, which is better known as crystal meth, and its effect also shows.

On the left, the chemical structure of 4-MMC. The CH3 group, bottom-left in the 4-MMC molecule, is moved to another bond point on the ring in 3-MCC. As mentioned, the molecule on the left is prohibited in the Netherlands, while the one on the right is not.

[/caption]In 2021, 3-MMC has been regularly in the news. According to the Trimbos Institute, the drug has been on the market since 2012, and there are clear signs that its use is increasing. 3-MCC falls under the Commodities Act, and is sold ‘for laboratory use’. It can easily be ordered, for instance on the internet. The chemical structures of 3-MMC and 4-MMC differ a little (see figure), but even a non-toxicologist would not be surprised to learn that the effect of the two substances is very similar, although there are some differences.

Increased use

3-MMC is a little cheaper than cocaine, costing about ten euros per gramme. Almost 10% of those questioned in a Trimbos Institute study say they have used the drug at least once over the last year. In 2018, the National Poisons Information Centre (NVIC) received ten questions about 3-MMC, the number increased to 25 in 2019, and in 2020 there were 64 questions. According to RTL-Nieuws, the police have also noticed an increase in the number of calls related to 3-MMC. The drug’s popularity among the young is particularly high in East Netherlands, according to Een Vaandag and RTV Oost. Based on a risk assessment of 3-MMC conducted by the CAM (Coordination Centre for Assessment and Monitoring of New Drugs), 3-MMC is expected to be placed on List II of the Opium Act in the autumn of 2021. New legal variants are already available on the internet, such as 3-CMC, in which the methyl group (-CH3) is replaced by a chlorine atom.

Wastewater analysis

In recent years KWR had regularly carried out research on the presence of drugs in the wastewater of three large Dutch cities. The research has so far focused on known drugs, such as cocaine, amphetamine (speed), methamphetamine (crystal meth), THC (cannabis) and MDMA (ecstasy), although an NPS has also been occasionally targeted.

3-MMC and 4-MMC cannot yet be well distinguished in today’s analyses. In the first inventory of measurements conducted in March 2020, we encountered these substances (probably mostly 3-MMC) in the wastewater of Amsterdam, the Eindhoven region and Utrecht.  Since the measurement method is extremely sensitive, we are able to measure low concentrations in the wastewater, representing very limited use – for example, a few grammes in a small municipality. The concentrations encountered are comparable to those of the closely related drug, methamphetamine (crystal meth). This suggests that the use of this drug is also comparable to that of crystal meth.

Wastewater analysis shows the use of 3-MMC/4-MMC, and thus provides a sensitive tool to detect the emergence of this – and other – designer drugs at a local and regional level, and to do so at an early stage.