The PMMA epidemic in Norway: Comparison of fatal and non-fatal intoxications

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Abstract

During a 6 month period (July 2010–January 2011) we observed 12 fatal intoxications and 22 non-fatal cases related to the drug paramethoxymethamphetamine (PMMA) in Norway (4.8 mill inhabitants). This toxic designer drug, also known as “Death”, is occasionally found in street drugs offered as “ecstasy” or “amphetamine”. The present study aimed to evaluate the cause of death, and to compare the PMMA blood concentrations in fatal and non-fatal cases. Methods for identification and quantification of PMMA are presented. The median age of fatalities was 30 years (range 15–50) with 67% males; in non-fatal cases 27 years (20–47) with 86% males. In the 12 fatalities, the median PMMA blood concentration was 1.92 mg/L (range 0.17–3.30), which is in the reported lethal range of 0.6–3.1 mg/L in peripheral blood and 1.2–15.8 mg/L in heart blood. In the 22 non-fatal cases, the median PMMA concentration was 0.07 mg/L (range 0.01–0.65). Poly-drug use was frequent both in fatal and non-fatal cases. The PMA concentrations ranging from 0.00 to 0.26 mg/L in both groups likely represented a PMMA metabolite. Three fatalities were attributed to PMMA only, six to PMMA and other psychostimulant drugs, and three to PMMA and CNS depressant drugs, with median PMMA concentrations of 3.05 mg/L (range 1.58–3.30), 2.56 (1.52–3.23) and 0.52 mg/L (0.17–1.24), respectively. Eight victims were found dead, while death was witnessed in four cases, with symptoms of acute respiratory distress, hyperthermia, cardiac arrest, convulsions, sudden collapse and/or multiple organ failure. In summary, all fatalities attributed to PMMA had high PMMA blood concentrations compared to non-fatal cases. Our sample size was too small to evaluate a possible impact of poly-drug use. A public warning is warranted against use and overdose with illegal “ecstasy” or “speed” drugs.

Introduction

The toxic designer drug paramethoxymethamphetamine (PMMA) is the 4-methoxy analogue of methamphetamine (MA). It is partly metabolized to the more well-known toxic drug paramethoxyamphetamine (PMA), which is the 4-methoxylated analogue of amphetamine (A) (Fig. 1). PMMA appeared later on the illegal drug scene than PMA, in the 1990s and 1970s, respectively. PMMA and PMA are sometimes offered on the clandestine market as a MDMA (methylenedioxymethamphetamine, “ecstasy”) substitute, often mixed with A, MA and/or MDMA. Both PMMA and PMA have abuse potential and are listed in many countries as substances controlled by legislation [1]. The effects mimic some of the psychological effects of ecstasy and “speed” (methamphetamine, amphetamine). However, the toxicity of PMMA and PMA, earning the street name “Death”, is reported to be substantially higher than with ecstasy and amphetamines, as documented by more than 90 fatal and many severe poisonings attributed to the ingestion of PMMA/PMA in Canada, USA, Australia and Europe [1]. As PMA and PMMA presumably account for only a small part of the apparent ecstasy ingestion, the relative number of fatalities is high [1], [2].

During a 6 month period (July 2010–January 2011), we observed the uncommon appearance in Norway (4.8 mill inhabitants) of several unnatural deaths in young adults, which were all apparently related to recent intake of A, MA or “ecstasy”. The fatalities were subjected to forensic autopsy and standard toxicological blood drug analysis, but no obvious cause of death was found. As there is little mortality attributable to A/MA when used alone, even in overdose [3], we performed supplementary analyses to search for other toxic agents, possibly related to amphetamines. This brought to light a Norwegian epidemic of fatal and non-fatal PMMA intoxications, which at the time of writing is still ongoing.

The present study aimed to evaluate the cause of death and to compare the PMMA blood concentrations in fatal and non-fatal cases. Methods for identification and quantification of PMMA will be presented.

Section snippets

Selection of cases

The Division of Forensic Medicine and Drug Abuse Research (DFMDA) at the Norwegian Institute of Public Health (NIPH) has the national responsibility for forensic toxicology analysis in biological specimens in all cases of suspected driving under the influence of drugs/alcohol (DUI), and in most cases of suspected unnatural death where the division serves 93% of the Norwegian population (except Mid-Norway). DFMDA receives blood specimens from about 9000 suspected criminal offences and 1600

Results

The median age of the 12 PMMA-related fatalities was 30 years (range 15–50) with 67% males, in the 22 non-fatal cases the median age was 27 years (20–47) with 86% males. Different geographical regions of Norway were represented both in fatal and non-fatal cases.

The postmortem specimens were collected median 2, range 1–6 days after death. The specimens were sent to DFMDA within median 5, range 2–9 days after autopsy.

The blood concentrations of PMMA, PMA, MA and A in fatal and non-fatal cases are

Comparison of blood drug concentrations in fatal and non-fatal cases

In the 12 fatal intoxications related to PMMA, the mean PMMA concentration in peripheral blood was 2.02 mg/L. In 11 of these fatalities, the PMMA concentrations were above 0.5 mg/L, and in most cases greater than 1.24 mg/L. These are high PMMA concentrations within the fatal range reported by other authors [1], [8], [9], [10], [11], [12]. For comparison, PMMA or PMA blood concentrations above 0.5 mg/L are reported to be associated with toxic and possibly lethal effects [13], [14]. In heart blood, a

Conclusion

The investigation of this large PMMA epidemic demonstrated that all fatalities attributed to the ecstasy-substitute PMMA had high PMMA blood concentrations, compared to non-fatal cases. Our sample size was too small to evaluate a possible impact of poly-drug use. A public warning is warranted against use and overdose with illegal “ecstasy” or “speed” drugs.

Acknowledgements

We are truly grateful for all the valuable scientific and analytical contributions and kind suggestions from our good colleagues Inge Morild, Sidsel Rogde, Kari Ormstad, Ilah Le Nygaard, Muhammad Al-Samarraie, Ritva Karinen, Liliana Bachs and Asbjørg Christophersen, and from Tormod Bønes and Ørjan Bye at NCIS/Kripos, and for the skilled routine work performed by colleagues at the DFMDA and the involved forensic departments which constitutes the foundation of the present publication.

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