Post-Mortem (Re)Distribution of 3,4-Methylenedioxymethamphetamine (MDMA, “Ecstasy”): Human and Animal Data

Abstract

In this paper, the distribution and redistribution of the amphetamine derivative, 3,4-methylenedioxymethamphetamine (MDMA, ecstasy) is brought into focus. Animal experimental data were compared with internationally reported MDMA-related human fatalities: in general, these turned out to be parallel with each other. Due to its inherent properties (e.g. significant volume of distribution), MDMA is liable to postmortem redistribution. Indeed, very high concentrations have been found in cardiac blood and tissues located centrally in the body (blood-rich organs such as lungs and liver in particular). This confirms that post-mortem redistribution due to diffusion from higher to lower concentration can easily take place, mainly at longer post-mortem intervals and when putrefaction occurs. Therefore, we can conclude that for post-mortem quantitation of amphetamine and derivatives, and MDMA in particular, peripheral blood sampling (e.g. femoral vein) remains compulsory. However, if the latter is impossible, MDMA quantification in a few alternative matrices such as vitreous humour and iliopsoas muscle may provide additional information to come to a reliable conclusion. Furthermore, it should be stressed that--at present--it is impossible to estimate the individual susceptibility to the various possible adverse effects of MDMA, which implies that it is impossible to provide a "safe" or "therapeutic" blood MDMA level. Therefore, in current forensic practice, the post-mortem pathological and toxicological findings should form an entity in order to draw a well-grounded conclusion.

How Postmortem Redistribution of MDMA in Acute Alcohol-MDMA Combined-Use Rats Change under Effects of Alcohol

“…Even combined with alcohol under less humidity, the (relatively minor) MDMA increases in vitreous humor levels cannot be due exclusively to dehydration, though the rise in creatinine concentration in vitreous humor at increasing postmortem interval due to dehydration has been confirmed 2 . As for the decrease in the latter period, it may be attributed predominantly to spontaneous chemical hydrolysis.…”

“…In this phenomenon, the concentration of drugs in the blood and other tissues can change up to 15-fold after death 12 . It is thought that all drugs will be affected to some extent by postmortem redistribution and the main contributing factors are (1) the time between death and sampling, (2) the site(s) of sampling (with femoral blood being the sample that is least affected by postmortem redistribution), (3) potential postmortem metabolism/production by either body enzymes or bacteria and finally, (4) physicochemical properties of the drug (such as pKa, LogP and most importantly volume of distribution (Vd)) 2, 13 .…”

“…In earlier interaction studies on postmortem data, the outcome measure has been drug concentration in the presence and absence of alcohol, rather than vice versa 2 . Additionally, the alcohol presence in biological specimens is a potential factor affecting analyses stability and its concentration, respectively 28 .…”

“…MDMA has a volume of distribution at steady state of 4.9 ± 2.6 L/kg, which belongs to substances having an apparent volume of distribution of more than 3–4 L/kg, and it is liable to postmortem drug redistribution 2 .…”

Effects of 3,4-Methylenedioxymethamphetamine Administration on Retinal Physiology in the Rat

“…Changes in light perception were demonstrated in humans after the administration of repeated doses of MDMA [17], [18], [19]. Moreover, the drug has been found in human vitreous humor after MDMA ingestion [20], [21], and vitreal MDMA quantification was proposed as a reliable way to measure the MDMA concentration for toxicological analysis [22]. Also, there are a few clinical case reports of ocular problems after MDMA ingestion [23], [24].…”