Drug Abuse

Europol–EMCDDA progress report on PMMA and PMA (9) in accordance with Article 3 of the joint action of 16 June 1997 concerning the information exchange, risk assessment and control of new synthetic drugs

Introduction

PMMA is a non-scheduled, new synthetic drug which has been found in association with PMA in �ecstasy’-like tablets. PMA has been listed in Schedule I of the 1971 UN Convention on Psychotropic Substances since 1986, and first appeared on the European market in December 1998. PMMA is regulated by law in four Member States: Germany (emergency scheduling List I of the Narcotics Act of 10 October 2000), Ireland (Schedule 1 of the Misuse of Drugs Acts, 1977 and 1981), Sweden (Ordinance SFS 1999:58) and the UK (Misuse of Drugs Act 1971, Class A).

PMA is a potent drug with amphetamine-like characteristics and is a potentially lethal substance. Found in �ecstasy’-like tablets, alone or in combination with MDMA, it has been associated with a number of deaths in Australia and, in combination with MDMA or PMMA, in the USA during the period 1998–2000. In the EU since July 2000, PMA has been implicated in a number of deaths that have occurred after ingestion by drug users of PMA in the form of �ecstasy’-like tablets, either alone (one case in Austria) or in combination with PMMA (four cases in Denmark and four cases in Germany) (10).

The association of PMMA/PMA became known to the authorities in the Member States in June 2000 when the Danish police arrested a man who was in possession of approximately 700 tablets with a �Mitsubishi’ logo, to be sold as �ecstasy’. He told the police he had already sold 300 of these tablets. On 18 July 2000, in the framework of Article 3 of the joint action on the early-warning mechanism on new synthetic drugs, Europol transmitted information received from the Danish authorities to the EMCDDA regarding the death of two 20-year-old men on 2 and 5 July 2000 and the hospitalisation of two more young people after the intake of �ecstasy’-like tablets with the �Mitsubishi’ logo. Laboratory analysis of the tablets that were found in the possession of the arrested man revealed that the tablets contained both PMA and PMMA. Based upon the autopsy findings, the forensic report stated that the presumed cause of the deaths in Denmark was acute intoxication with PMA and PMMA in one death, and with PMA, PMMA and MDMA in the other. The EMCDDA was later informed by the Danish Reitox national focal point about the death of a third, 24-year-old man on 2 September 2000 which, according to the final forensic report, was most probably caused by acute intoxication with PMA and PMMA.

Available information on PMMA and PMA

Chemical and physical description, including the names under which PMMA and PMA are known

Figure 1: Chemical structure of PMMA

The molecular formula of PMMA is C11 H17 NO. Known as 4-methoxymethylamphetamine (4-MMA in Shulgin’s Pihkal (Shulgin, 1991)) or by the acronym PMMA, its full chemical name is N-methyl-1-4-(methoxyphenyl)-2-aminopropane. PMMA is a structural hybrid of PMA and methamphetamine (11) (Figure 1). PMMA is commonly encountered in the form of tablets. Street names for PMMA/PMA tablets in Austria are �killer’ and �red Mitsubishi’. Tablets seized in Austria, Germany and Spain were white, red, beige or brown in colour, and marked with �E’ or �Mitsubishi’.

Figure 2: Chemical structure of PMA

The molecular formula of PMA is C10 H15 NO. Known as 4-methoxyamphetamine (4- MA) or by the acronym PMA, its full chemical name is 1-(4-methoxyphenyl)-2- aminopropane. PMA is a methoxylated amphetamine derivative (Figure 2).

From 1972 to 1973, PMA was sold in the USA and Canada in powder form, sometimes in capsules, under the street names �Chicken yellow’, and �Chicken powder’, and often sold as MDA. Since the mid-1990s, PMA in �ecstasy’-like tablets has been believed by users to be MDMA. PMA has been encountered in the EU in powder and tablet form. Reported street names in Austria are �Death’ and �Red Mitsubishi’, and �Mitsubishi double-stack’ in the USA. Tablets seized in France and the UK were white or beige in colour, marked with �Superman’ or �Elephant’.

The frequency, circumstances and/or quantities in which PMA/PMMA is encountered

Information received by the EMCDDA

Nine EU Member States (Belgium, Denmark, Germany, Spain, France, the Netherlands, Austria, Sweden and the UK) have reported seizures of PMA or PMA/PMMA and/or have encountered these substances in toxicological tests (Belgium, Spain, Austria) or in pill-testing programmes (e.g. the �Check-it!’ programme in Vienna).

In July 2000, the Austrian Reitox national focal point reported on the death of a 17-year-old man. Forensic analysis confirmed that PMA was involved in his death. Austrian police investigations relating to this death led to the seizure of 4 478 tablets of PMA, all with the �Mitsubishi’ logo. The colour of 1 785 of these tablets was white and 2 693 were red-brown. On 16 September 2000, PMA/PMMA was found for the first time during a �Check It!’ pill test at a rave party in Vienna. After the analysis of 48 tablets being sold as �ecstasy’, four were found to contain 400 mg of PMA in combination with PMMA and amphetamine. The tablets were red in colour, had the �Mitsubishi’ logo, and were 7 mm in diameter and 5 mm thick. They weighed 230 mg each and had a cylindrical shape. On 7 October 2000, the EMCDDA was informed of the detection of another PMMA/PMA tablet found at a rave party in Vienna by �Check-it!’ testing. The logo was a very deep stamped �E’. The tablet was white and had the same physical characteristics, in terms of shape, diameter, thickness and weight, as the tablets analysed in September. The tablet contained 40 mg of PMMA and 20 mg of PMA, with small amounts of amphetamine or ephedrine. All tablets detected in Austria were sold as �ecstasy’.

The Danish Reitox national focal point reported three deaths associated with PMA/PMMA, which occurred between 2 July and 2 September 2000. In Denmark, tablets seized in July 2000 were marked with the �Mitsubishi’ logo, were light brown in colour, 7 mm in diameter, weighed 280 mg and did not have a break line. Between 29 June 2000 and 7 March 2001, there were 16 more seizures of a total of 1 384 PMA/PMMA tablets. The largest seizure consisted of 843 tablets, which were seized in Copenhagen on 15 January 2001. According to laboratory findings, tablets in 14 of the 16 seizures were beige in colour, marked with the �Mitsubishi’ logo and were 7 mm in diameter, 5.1 mm thick and 230 mg in weight, on average. Five tablets contained ephedrine in addition to PMA and PMMA. In the other two seizures, the tablets seized were white with an undefined logo and weighed 88 and 139 mg, respectively.

At the beginning of July 2000, Europol received information from the BKA about three tablets seized in Friesland in northern Germany containing PMMA/PMA. The same information was transmitted to the EMCDDA by the German Reitox national focal point using a Europol–EMCDDA reporting form for new synthetic drugs. The tablets carried the �Mitsubishi’ logo, were 7.2 mm in diameter, 5.1 mm thick, weighing 220 mg with a break line on the back. Europol reported one death after the use of such a tablet. One year before, in July 1999, an illicit laboratory had been dismantled in Brandenburg, Germany, where small amounts (<10 g) of PMA and PMMA were discovered. The German Reitox national focal point reported that PMA was also suspected of being involved in the death of an 18-year-old woman in November 2000, according to the Land criminal police office (LKA) of Rhineland-Pfalz.

The French Reitox national focal point reported on the results of toxicological analyses which demonstrated the presence of PMA in samples (five tablets, two powders).
The samples were encountered in February 2001 in the Aquitaine region in the southwest of France and in Bourgogne, Champagne and Franche-Comté in the east of France. This was the first time that PMA was identified within the French Système national d’identification des toxiques et substances (Sintes) system. Tablets had the �Superman’ logo, were white or beige, scored, 8.1 mm in diameter, 4.9–5.0 mm
thick and weighed 299–308.8 mg. They contained PMA in combination with either MDMA, MDA or DMA (dimethoxyamphetamine). The powders were white and contained PMA, chloroquine and MDA.

The Spanish Reitox national focal point reported that tablets without logos containing PMMA had been analysed in 2000: six brown tablets with PMMA, caffeine and procaine in Tarragona, Cataluña on 28 August 2000, five brown tablets with PMMA in San Sebastian on 22 September 2000, and a number of white tablets with PMMA and caffeine in Tarragona on 13 October 2000.

The Belgian Reitox national focal point reported on a non-fatal emergency in April 2001 when PMA, together with MDMA and MDA, was detected in the urine sample of a 17-year-old girl brought to the emergency care unit.

The Swedish Reitox national focal point notified that there were two seizures of PMA in 1998 (12) and four seizures of PMA/PMMA as well as three seizures of PMA between March and November 2000. The largest seizure took place in Stockholm on 9 November 2000 and consisted of 1 782 PMA/PMMA tablets. Amphetamine and methamphetamine were also found in some of the other seizures.

The United Kingdom Reitox national focal point reported on the seizure of 14 white PMA tablets (8.1 mm by 4.7 mm, weighing 295 mg) in Leicestershire on 16 November 2000. Analysis by the Birmingham laboratory of the forensic science services revealed that they each contained 31 mg of PMA and 20 mg of MDMA, as well as caffeine. The tablets were marked with an �elephant’ logo facing right on the flat surface opposite a half-scored convex face. They were identical to tablets identified in the Netherlands in late 2000.

The Dutch Reitox national focal point informed on the seizure of 119 tablets in 2000, containing PMA, MDMA and traces of MDEA and caffeine. In the Drugs Informatie en Monitoring Systeem (DIMS) report 1998–2000, it was indicated that two tablets containing PMA/PMMA were detected by the DIMS system in 2000.

Information received by Europol

The Europol national units of Austria, Denmark, Germany, the Netherlands and Sweden have reported seizures of tablets containing PMMA, with or without PMA, to Europol. The reported seizures are mentioned in Table 1. In addition, the German BKA provided reports of seizures of PMMA/PMA in France. Nine Member States (Belgium, Greece, Spain, Ireland, Italy, Luxembourg, Portugal, Finland and the UK) have reported that, as yet, they have not seized any PMA and/or PMMA.

(a) = sample only; the exact size of the seizure was not reported. Source: EuropolEMCDDA progress report (2564132).

The Austrian National Europol Unit reported the seizure of 4 478 tablets with the �Mitsubishi’ logo containing the active substances PMA and PMMA. These tablets were part of a 5 000 tablet shipment from a Polish citizen. A further 10 000 tablet shipment was planned for September 2000. On 17 October 2000, a Polish citizen was arrested after supplying 10 000 tablets with the �E’ logo containing the active substance PMA/PMMA. These tablets were smuggled by car from Poland to Austria.

The Danish National Europol Unit reported 10 seizures of tablets containing PMA/PMMA. The size of the seizures varied between 1 and 718 tablets.

The German BKA reported six seizures of tablets containing PMA as the active substance. The BKA stated that four of the six seizures were made after a user died after taking one or more tablets and that, on 7 November 2000, another victim died after taking five tablets. Further investigation led to the arrest of a supplier in possession of 18 tablets containing PMA and MDMA as active substances, in addition to 974 �ecstasy’ tablets, 100 LSD trips, 10 g of amphetamine and 7 g of herbal cannabis. The 18 PMA/MDMA tablets seized were part of a delivery of 1 000 tablets bearing the logo �Mitsubishi’. In addition, the BKA reported information from the French Observatoire Français des drogues et des toxicomanies (OFDT) to Europol. The OFDT reported the results of the analyses of seven samples (five tablets with the logo �Superman’, and two powders) from seven investigations. PMA was detected in all the samples, MDMA in two and DMA in five of the samples.

Investigations by the BKA established that there was a relationship between the seizures in Austria, Denmark, Germany and Poland. The Polish authorities raided two illicit laboratories in December 2000, resulting in the arrest of four people. Inside these two laboratories, equipment, including two tableting machines, and chemicals were found. Further investigations demonstrated no relationship between the seized tablets and the two tableting machines. According to information from the Polish authorities, production of PMA and/or PMMA continues to take place in Poland. Further BKA investigations showed that tablets seized in Austria, Denmark Germany and , with the logo �Mitsubishi’ and �E’, were all from the same source.

The Dutch unit for synthetic drugs reported the seizure of 119 tablets containing PMA, bearing the logo �Elephant’, on 25 October 2000. After an exchange of information with the German authorities, in January 2001 the Dutch authorities seized a further 5 000 tablets, also with the logo �Elephant’ and containing PMA and MDMA. According to a report from the German BKA, there was no forensic link between the tablets with the �Elephant’ logo and the �Mitsubishi’ tablets that were seized.

The Swedish National Europol Unit reported a total of nine seizures of PMA in 2000. In eight of the cases, the quantities seized were limited, varying between 1 and 19 tablets per incident. In one case, however, 1 782 PMA tablets were seized. PMMA was also detected in seven of the cases and, in addition, traces of amphetamine and/or methamphetamine were present in four of the cases.

The results of investigations by the Drugs Enforcement Administration (DEA) in the USA were compared with details of seizures (logos �Mitsubishi’ and �E’) in the EU, which demonstrated that tablets seized in the USA came from the same source as tablets seized in Denmark. Similar tablets seized in Canada are also suspected to be from the same source. According to the BKA, there is a high probability that all tablets with PMA/PMMA plus the logo �Mitsubishi’ and �E’ seized worldwide come from the same source. Tablets with the logo �Elephant’ are thought to be from a different source.

In summary, seizures were made in six Member States of tablets carrying the logo �Mitsubishi’, �Elephant’, �E’ and/or �Superman’. Almost all of the tablets with the �Mitsubishi’ or �E’ logo contained both PMA and PMMA. The trafficking of PMA/PMMA tablets has occurred in three Member States. There were no recorded PMA/PMMA tablet seizures reported in nine of the Member States.

Investigations undertaken by the German BKA proved a relationship between the seizures in Austria, Denmark, Germany and Poland. Further BKA investigations showed that all the tablets containing PMA/PMMA bearing the logo �Mitsubishi’ or �E’ that were seized in Austria, Denmark, Germany and the USA came from the same source.

With the exception of one laboratory discovered in Germany in 1999, where small amounts of PMA and PMMA were produced, no Member State has any information regarding the production of PMA and/or PMMA in the EU. Two illicit laboratories have been detected and dismantled in Poland. The number of seizures during the period 2000–01, in particular in Denmark, however, suggest the involvement of organised crime in the production and trafficking of PMA and PMA/PMMA tablets sold as �ecstasy’.

A first indication of the possible risks associated with PMA/PMMA

Taking into account the fact that PMMA was found in combination with PMA in almost all cases, it seems necessary to consider the possible risks of using these substances separately as well as when associated together in tablets sold as �ecstasy’.

PMA

In the EU, PMA has been involved in one death in Austria in July 2000. No clinical data are yet available on this case. There has also been a PMA-related death in Spain, in 1995.

There were a number of earlier cases in 1973 where PMA was involved in nine deaths in Ontario, Canada. At that time, PMA was not sold as �ecstasy’ but usually as MDA, in a powder form. Australian reports suggest that PMA has been involved in 11 to
12 deaths from 1997 onwards, sold as �ecstasy’. PMA sold as �ecstasy’ has reappeared in Canada and in the USA, since February 2000. In the USA, several deaths were attributed to PMA in 2000 (Erowid web site, 2000).

A 50 mg PMA tablet induces a �high’ by increasing the pulse rate and blood pressure (BP) and by giving the user a feeling of well-being. Doses as low as 60 mg can cause significant increases in BP, body temperature and pulse. Larger doses can cause irregular heartbeats, heart attacks, breathing difficulty, kidney failure, convulsions, coma and
death. Blood concentrations of more than 0.5 mg/l seemed likely to be associated with toxic effects. Death generally occurs when body temperatures rise so high that the central nervous system shuts down. The causes of death from PMA included documented hyperthermia in three cases (temperatures of 41.5–46.1 oC), with features of hyperthermia in one other case and intracranial haemorrhage in another.

In comparison with MDMA’s immediate physiological response, PMA is known to have a delayed onset of action (around one hour). A possible consequence of this difference is that users may take several tablets of PMA when the expected effects are delayed or seem to be weaker than those of MDMA.

PMMA

There has been one PMMA-related death in Spain, in 1993. No other fatal or nonfatal emergencies involving PMMA alone have been reported to the EMCDDA or to Europol.

Discrimination studies on rats and mice have shown that PMMA lacks both amphetamine-like stimulant effects or hallucinogenic-like qualities but, being several times more potent than MDMA as a discriminative stimulus, it may be a prototypic parent for the MDMA family of designer drugs (Glennon et al., 1988, 1997). In other studies, comparisons between the neurotoxicity potential of PMMA, PMA and MDMA suggest that PMMA, like PMA and MDMA, produces long-term (possibly neurotoxic) effects on brain neurones, but that PMMA is less potent than MDMA as a 5-HT neurotoxin (Steele et al, 1992).

PMA/PMMA

According to the German BKA, PMA and PMMA combinations have been involved in nine deaths in the EU: four in Germany, four in Denmark and one in Austria. The final forensic reports from Denmark confirmed that two of the deaths were probably caused by acute intoxication with PMA and PMMA and one death by acute intoxication with PMA, PMMA and MDMA. All victims were believed to have taken between two and five tablets bearing a �Mitsubishi’ logo, which were sold as �ecstasy’.

According to the clinical reports, intoxication often resulted in an increase of body temperature (up to 41.5–46 oC) which, in the worse cases, will shut down the brain and vital organs, resulting in death.

Studies in pharmacology and biochemistry indicate that PMMA produces some of the MDMA-like effects that PMA is lacking, whereas PMA has somewhat amphetamine-like characteristics but no MDMA-like characteristics (Dal Cason, 2000). This feature may reinforce the first impression to users of having consumed a low dose of �ecstasy’. This subjective effect, combined with the delayed onset of action of PMMA/PMA, may encourage some users to take multiple doses with a major risk of overdose.

One hypothesis about the PMA/PMMA association is that, by combining PMA and PMMA in fake �ecstasy’ tablets, illicit manufacturers selling the tablets aim to simulate the MDMA effects expected by users. It is also noteworthy that substituting PMA or PMA/PMMA for MDMA could be more cost-effective for illicit producers and may also present fewer risks. In fact, the precursors for PMA/PMMA are easier to obtain and less strictly controlled by legislation than those for MDMA.

Chemical precursors

The most recent synthesis of PMMA was performed by the DEA north central laboratory through catalytic hydrogenation of the precursor 4-methoxyphenylacetone (paramethoxyphenyl -2 -propa none (PMP2P)). Other precursors and reagents quoted in Shulgin’s Pihkal (Shulgin, 1991) are methylamine hydrochloride, sodium cyanoborohydride, ethyl chloroformate and formic acid.

Precursors for PMA (13) and PMMA are widely available commercially.

Mode and scope of established or expected use of PMA/PMMA as a psychotropic substance

Illicit use of either is rare. Both are sold as MDMA. Several reports in the EU and the USA suggest that the �rave’ environment could be the main target for PMA/PMMA sold as �ecstasy’ by drug dealers. Users in France said that PMA tablets with the �Superman’ logo were usually easy to obtain. However, Internet sources imply a limited appeal for deliberate use of PMA and PMMA. Internet health warnings focus on the danger of relatively low doses of PMA or PMMA, especially when mistaken for �ecstasy’, and of more than 60 mg being consumed, according to �ecstasy’ patterns of use.

Other uses of PMA/PMMA and the extent of such use

There is no legitimate medical use of either PMA or PMMA.

 

 

(9) Europol file 2564-132.

(10) Following a recent toxicological review of deaths in Spain, the Spanish Reitox national focal point informed us that PMMA was detected in one death in 1993 and PMA was detected in one in 1995.

(11) The ethyl analogue of PMA, N-ethyl-4-methoxyamphetamine, has been detected in a urine sample in Belgium.

(12) On 23 December 1998, two seizures of PMA were notified by the Europol national unit in Sweden using the reporting form for new synthetic drugs.

(13) PMA is available from Sigma Chemicals, catalogue No M 3404.

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