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This resource is part of EU Drug Market: Methamphetamine — In-depth analysis by the EMCDDA and Europol. 1-Boc-3-Carbamoylpiperidine
There are many ways to make methamphetamine, and each has its own risks and advantages. In Europe, two main methods exist, classified according to the chemicals used as starting materials, known as precursors. One method is based on ephedrine or pseudoephedrine which can be imported in bulk powder or extracted from medicinal products or even from ephedra plants. This method is hazardous and difficult to scale up; in Europe, it is mostly used in small- to medium-scale ‘kitchen’ laboratories in and around Czechia, where precursors extracted from medicines are typically used. This method produces the potent d-isomer form of methamphetamine (d-methamphetamine (1). The other method uses BMK (also called benzyl methyl ketone, or phenyl-2-propanone, ‘P-2-P’), an oil that can be imported to the EU or made in Europe from chemicals known as designer precursors (also called pre-precursors). This method is more amenable to scaling up and is therefore suitable for use in industrial-scale laboratories, as has been observed in the Netherlands and Belgium. Its main disadvantage is that the resulting product is a 50:50 mixture of the d- and l-isomers, the l-methamphetamine being a less desirable product. This means an additional step is needed at the end of the synthesis to separate and purify the potent (hence preferred) illicit product: d-methamphetamine. Techniques to perform this separation have been used in illicit production laboratories in Mexico since at least 2009 (INCB, 2017) and more recently in the Netherlands and Belgium. Recent data also shows that European BMK-based laboratories have further increased the efficiency and output of production by recycling the unwanted l-methamphetamine to obtain more d-methamphetamine for each litre of BMK used (see Section Recycling unwanted by-product: a game-changer in methamphetamine production).
BMK has limited legitimate uses; in Europe it is mostly used to produce amphetamine, and increasingly, for the production of methamphetamine. BMK may be imported to the EU but it is more often produced locally from pre-precursors.
BMK methods typically involve the catalytic reduction (reductive amination) of an intermediate formed between BMK and methylamine. In Europe, there are two main techniques: (1) reductive amination uses the ‘aluminium amalgam method’; (2) the ‘high pressure method’ is the same technique used to produce MDMA in Europe, the only difference being the starting material (the precursor), where BMK yields methamphetamine and PMK (piperonal methyl ketone, also known as methylenedioxyphenyl-2-propanone, ‘MDP-2-P’) yields MDMA.
In 2020, seven EU Member States seized close to 5 600 litres of BMK, most of which (75 %) was reported by the Netherlands (4 200 litres). These are globally relevant amounts, with only Mexico reporting larger seizures in 2020 (11 000 litres seized), according to the INCB (2020).
Importantly, these values need to be considered in the context of the close to 35 tonnes of various pre-precursor chemicals seized in the EU in 2020, which could be used to produce significant additional amounts of BMK, often in dedicated ‘conversion’ laboratories. These pre-precursors include APAAN, glycidic derivatives of BMK, APAA and MAPA, all of which were successively introduced in the market as soon as legal controls were applied to their predecessors (see Figure Quantity of designer precursors for the synthesis of BMK seized in Europe). In 2020, five Member States reported combined pre-precursor seizures of over 1 tonne. These were Belgium (12 tonnes), Germany (almost 8 tonnes), Hungary (7 tonnes), the Netherlands (less than 7 tonnes) and France (1 tonne). Whenever the origin of the seizures was outside the EU (68 % of the quantity seized), the consignments originated in China (including Hong Kong) and were typically misdeclared as chemical industrial products or other commercial goods.
In Europe, the rapid replacement of pre-precursors has been particularly evident since 2011, when information exchange between international authorities was enhanced, leading to more effective precursor diversion control worldwide (EMCDDA, 2019a). To avoid disruptions to the steady supply of precursors for illicit laboratories, producers quickly changed from the scheduled precursor BMK to APAAN, which then became one of the most seized pre-precursors from 2012 to 2014. The scheduling of APAAN in 2014 led to the appearance of glycidic derivatives of BMK, quickly followed by APAA which took the lead in seizures from 2016 to 2018. APAA was scheduled in 2019, leading to the emergence and prevalence of MAPA in seizures during 2019 and 2020. MAPA was then scheduled in late 2020, and in that same year, EAPA (the ethyl analogue of MAPA) was seized for the first time in Europe. These data illustrate the ingenuity and adaptability of synthetic drug producers: the declining seizures of one pre-precursor are accompanied by the concomitant rise of another (see Figure Quantity of designer precursors for the synthesis of BMK seized in Europe).
Source: European Commission. The source data for this graphic is available in the source table on this page.
The availability of BMK and BMK precursor alternatives in Europe, although important, only provides an indication of the overall capacity to produce amphetamine-based stimulants. However, the manufacture of methamphetamine requires additional production steps, the chemicals required for which can provide more information on the trends and scale of methamphetamine production in Europe.
BMK methods produce 50:50 mixtures of d- and l-isomers of methamphetamine (a racemic mixture) (Maxwell and Brecht, 2011). To extract d-methamphetamine from the mixture, it can be treated with an ‘optically pure’ substance, and typically tartaric acid is used. This process is called ‘resolution’ and reduces the overall yields of the synthesis to 50 %. This type of separation process is well known to Mexican synthetic drug producers, and tartaric acid has been seized in association with drug production in Mexico since at least 2009 (INCB, 2019).
In 2020, almost 18 tonnes of tartaric acid was seized in Europe, (see Figure Quantity of tartaric acid seized in Europe). Theoretically, this would be enough to separate up to 36 tonnes of a racemic mixture of methamphetamine, resulting in a potential yield of up to 18 tonnes of d-methamphetamine.
These data confirm what has been found in illicit laboratories: that large quantities of methamphetamine are being produced in Europe in industrial-scale laboratories, using methods associated with Mexican methamphetamine producers.
Large seizures in 2020 of the methamphetamine-specific adulterant, methylsulfonylmethane, provide additional evidence of an increase in the processing of the drug in Europe that year. Methylsulfonylmethane (also known as methyl sulphone or dimethyl sulphone) is ideally suited to adulterate crystal methamphetamine because, during processing as the mixture recrystallises, it resembles pure crystal methamphetamine (EMCDDA and Europol, 2016). Seizures of methylsulphfonylmethane were rarely reported in the European database of precursors until 2020, when the Netherlands reported four seizures totalling more than 2 tonnes; the large majority of which appears to have been made in a single seizure at an illicit laboratory.
Source: European Commission. The source data for this graphic is available in the source table on this page.
Previously, when the d-methamphetamine was separated using tartaric acid, the leftover material containing the l-isomer was regarded as an unwanted by-product to be discarded. Illustrating the continuous drive to improve efficiency and profits, illicit drug producers in Europe have introduced new methods to reconvert these discarded solutions back to a racemic 50:50 mixture of d- and l-methamphetamine, from which the d-methamphetamine can be separated using tartaric acid. These recycling procedures explain the record quantities of tartaric acid seized in Europe (see Figure Quantity of tartaric acid seized in Europe).
This process can be repeated several times: each time a fraction with the unwanted l-methamphetamine is produced, it can be reconverted (‘racemised’) back to a mixture and the d-isomer separated until the waste cannot be further recycled. The process, called ‘RRR’ (resolution-racemisation-recycling) (see Figure Processing of methamphetamine: resolution-racemisation-recycling), is a standard technique used in the pharmaceutical industry to increase production yields of medicines where only one isomer is pharmaceutically active (Astleford and Weigel, 1997). The RRR technique increases the yield of d-methamphetamine from BMK from 50 % to 75 % after one iteration, up to 87.5 % on the second iteration and 93.75 % by the third. The racemisation of the discarded solutions of l-methamphetamine is triggered using small amounts of a chemical such as AIBN (or another radical initiator) and a source of thiyl radicals (for example methyl thioglycolate, thioglycolic acid or dimyristyl peroxydicarbonate) (Escoubet et al., 2006; Yerande et al., 2014). AIBN has a low decomposition temperature, can easily ignite and its use presents a risk of explosion (National Center for Biotechnology Information, 2022).
Data reported to the European Commission indicates that in 2020, 327 kilograms of AIBN, 525 kilograms of methyl thioglycolate, 248 kilograms of dimyristyl peroxydicarbonate and 2.5 litres of thioglycolic acid were seized in Europe. Partial data available for 2021 indicate seizures of 19 kilograms of AIBN, 90 kilograms of methyl thioglycolate, 139 kilograms of dimyristyl peroxydicarbonate and 20 litres of thioglycolic acid. All seizures occurred in the Netherlands and some were seized during the dismantling of illicit laboratories. Information reported by Dutch police to the EMCDDA indicates that at least one shipment of 13 kilograms of AIBN in 2021 originated in Mexico. As well as indicating the level of sophistication involved, bearing in mind that these reagents are required in small amounts (relative to the quantity of methamphetamine being treated), the quantities seized provide further evidence of the scale of methamphetamine production using BMK methods in Europe. They also show that combining the expertise of Mexican and Dutch drug producers and applying techniques from the pharmaceutical industry has maximised production efficiency.
Until the advent of methamphetamine production based on BMK in the Netherlands and Belgium, European production of methamphetamine was mostly based on ephedrine or pseudoephedrine precursors; this is still the method typically found in small- to medium-sized laboratories in Czechia and neighbouring countries (most often using the ‘Nagai method’) and also involves the use of iodine and red phosphorous. When in powder form, these precursors are regulated at international and EU level, but they can also be obtained from over-the-counter medicinal products, which takes them out of the scope of precursor legislation (Council of the European Union, 2013), and presents challenges for enforcement. Restrictions have been put in place to tackle multiple purchases of the medicines at national level in Czechia and more recently Germany and Poland, but the lack of a harmonised approach at EU level often results in trafficking from countries with less stringent regulations to those where production occurs (or from outside the EU).
Ephedrine and pseudoephedrine can be chemically reduced using a variety of agents (2). Starting from ephedrine or pseudoephedrine has the advantage that the product obtained is d-methamphetamine, so there is no need to go through the RRR process. However, there are several factors that make this method difficult to scale up, including challenges in obtaining the bulk precursor or the strictly controlled medicines; extracting sufficient quantities of precursor from the medicines; safely controlling the chemical reactions to avoid explosions; and obtaining good enough yields after the purification and crystallisation processes. Hence, production via this method in Europe usually operates at capacities less than 50 grams (see Section Methamphetamine production facilities dismantled in the EU).
In 2020, 38 seizures amounting to 8 kilograms of ephedrine and 107 seizures amounting to 234 kilograms of pseudoephedrine were reported by 12 Member States. Poland seized close to 70 % of the EU total, which included pseudoephedrine preparations, i.e. medicines (mostly shipped from the United Kingdom) and pseudoephedrine raw material, i.e. powder (reported as intra-EU trade). In 2019, two thefts of pseudoephedrine (raw material and hydrochloride) amounting to 536 kilograms were reported by Germany, indicating that attempts to obtain pseudoephedrine for methamphetamine production go beyond trafficking and diversion.
In 2020, seizures of other chemicals associated with the production of methamphetamine from ephedrine and pseudoephedrine, including red phosphorus, iodine, hydriodic acid, hypophosphorous acid and phosphorous acid, were typically modest and made at local level. Action to prevent the diversion of red phosphorus for methamphetamine production was taken in 2020, when it was added to the EU regulations governing drug precursors (Council of the European Union, 2020). In some incidents, seizures were made in small methamphetamine laboratories in Czechia, but also in Germany, Italy, the Netherlands, Austria and Slovakia.
The available data on the number of seizures and the quantities of ephedrine, pseudoephedrine and associated chemicals seized in Europe did not change significantly from 2015 to 2020, beyond the expected natural fluctuations (see Figure Quantities of ephedrine and pseudoephedrine seized in Europe), despite the large increases in seizures of methamphetamine in Europe. This supports the view that the current ‘creeping’ market expansion is not related to the ephedrine/pseudoephedrine method, but rather the BMK methods.
Source: European Commission. The source data for this graphic is available in the source table on this page.
Synthetic drug production poses a number of possible hazards. In the last few years, a number of fatalities have been recorded in synthetic drug production laboratories in the Netherlands and Belgium due to fires or explosions (van den Berg, 2021) or suffocation from carbon monoxide or other toxic fumes caused by the production process (Steenberghe, 2020). A scientific review of cases of exposure to chemicals in illicit drug laboratories linked the exposure not only to mild or moderate respiratory, ocular and dermal effects, but also to severe symptoms and fatalities (Koppen et al., 2022). As with all synthetic drug production, the manufacture of methamphetamine does not just pose hazards to those involved in production; it also leads to the generation of chemical waste products, which are typically dumped away from the production site (but within a reasonable radius). Given the location of many laboratories, this can mean in a neighbouring country, such as Belgium, Germany or the Netherlands. Europol information also suggests that people that supply clean chemicals to illicit laboratories may collect the waste for disposal at locations far from the production zone. Such techniques can frustrate efforts to identify production sites and present collateral risks for the environment and people involved.
One kilogram of methamphetamine produced using the red phosphorus method generates 5-6 kilograms of waste (Europol, 2019). Waste is also produced when methamphetamine is produced from BMK, and when BMK is produced from designer precursors. This results in environmental damage, health risks and high clean-up costs. A variety of methods are used to dispose of the large quantities of chemical waste created during synthetic drug production. For example, the waste may be simply poured down the sink or toilet, although this is likely to be rare, as the waste can be corrosive or so viscous that it would block the drains. If chemical waste is disposed of in this way, it may affect the quality of drinking water or adversely affect municipal wastewater treatment plants (Schoenmakers et al., 2016). More commonly, members of the public report containers of waste dumped in the countryside, and there have also been instances where waste has been found buried underground. Waste can also be left in abandoned property or loaded into stolen vans or lorry trailers, which may then be set on fire to conceal forensic evidence. More elaborate methods have been found, including the use of modified vans that pump waste onto road surfaces. Six dumping sites specifically related to methamphetamine were reported in 2020 two in Belgium, related to dumping of equipment, and four in the Netherlands. Since methamphetamine in those countries is mainly produced using BMK, it is not always possible to determine whether the dump sites are related to amphetamine or methamphetamine production.
Knowledge of the mechanisms and extent of environmental damage related to synthetic drug production is fragmented and this is an under-researched area. While there are stand-alone studies on specific impacts, a more comprehensive and complete assessment of the environmental impact of synthetic drug production has not yet been done. Researchers in Czechia found that the presence of methamphetamine in wastewater leads to indications of dependence and behavioural changes among fish, disturbing mating habits and potentially impacting the aquatic ecosystem (Horký et al., 2021). A better understanding is needed of the impact of methamphetamine production waste and methamphetamine residues on biodiversity and the environment.
(1) d-methamphetamine is also known as (S)-(+)-methamphetamine, whereas l-methamphetamine is also known as (R)-(–)-methamphetamine. (2) These typically include non-metal reductions using hydriodic acid and red phosphorus, metal reductions such as the ‘Birch’ reduction, or reductions using palladium or platinum heterogeneous catalysis (‘Emde method’). Additional reduction methods exist but are rarely encountered (UNODC, 2006).
Consult the list of references used in this resource.
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