First the ecstasy and then comes the agony

There have been several reports in the media recently of deaths resulting from what has been described as a “bad batch” of ecstasy. As a pharmacologist several alarm bells rang when I read these reports and so I looked into it a little deeper.

The general premise is that a rouge batch ecstasy tablets containing a toxic contaminant called PMMA have found their way onto the elicit drug’s market. The recent deaths are being attributed to the presence of PMMA but little is being reported on the intrinsic dangers of ecstasy itself. 

The chemical name of ecstasy is N-methyl-3,4-methyl enedioxy-amphetamine (otherwise known as MDMA).  The chemical name of the PMMA contaminant is para-methoxy-N-methylamphetamine, which has arisen, it is claimed, as a by-product of poor chemical synthesis.  The news story is reminiscent of the TV series, Breaking Bad and paints an image of a semi-competent Jesse Pinkman type character cooking up a batch of MDMA that would drive Walter White into a fit of rage because the temperature of the vat was half a degree out. (For the record, crystal meth of Breaking Bad fame and MDMA are chemically quite different). 

Personally, I am rather skeptical that the presence of PMMA is a result of incompetent synthesis. It seems more likely that it originates from one of the starting materials in MDMA’s manufacture.  In other words, it’s there from the start and once in the mix, it’s rather hard to remove unless the MDMA is manufactured in a modern, well equipped laboratory.  Perhaps this particular “cook” is not such an inept chemist after all, but whoever is sourcing the chemicals for the synthesis might consider a better quality control policy.

The other myth that has appeared in a few places, or at least is implied, is that ecstasy itself is a safe drug and it’s only the presence of the PMMA that is leading to the deaths.  Whereas the source of the PMMA is a matter of academic speculation the story that ecstasy in its pure form is safe is really quite perniciously dangerous.

MDMA started off as its close relative MDA, in the 1950s as a cough suppressant and it was once tried out as a weight loss drug. Development of MDMA for these uses soon stopped however, because of the inherent risks involved. MDMA and its derivatives work by increasing the release of several monoamine neurotransmitters including serotonin, noradrenaline and dopamine in the brain.  The increase in neurotransmitters leads to the well known effects of MDMA notably, increased wakefulness, a sense of energy, sexual arousal, and postponement of fatigue and sleepiness. The trouble is that tinkering with one area of highly complex brain chemistry inevitably results in ripple effects elsewhere.  In the case of MDMA, it messes up the brain’s temperature control mechanisms and can lead to a syndrome called hyperpyrexia, which essentially means the body temperature increases uncontrollably.

The dangers of hyperpyrexia is the reason why consumers of MDMA are advised to keep hydrated.  Such simple advice has some merit but unfortunatelysince the feedback mechanisms of the brain are messed up it’s not uncommon to over-compensate and drink too much.  Drinking too much water in a short period of time dilutes the body’s electrolytes and that in itself can be fatal.

The dangers don’t stop there, far from it, because consumers of MDMA are also playing a game of genetic Russian roulette. MDMA is removed from the body mainly by an enzyme with the snappy name of CYP 2D6.  The CYP denotes that it’s a member of the cytochrome P450 enzyme family, by far the most important mechanism the body has for removing toxins. About 7% of the caucasian population however, are genetically deficient in CYP 2D6.  These people find it hard to remove MDMA from the body and so they overdose much more readily than others that might have taken the same dose. CYP 2D6 is so notorious for causing these types of problems that pharmaceutical development conducts specific tests to see if this enzyme is involved in the removal of any particular drug.  If it is, then there’s a chance that the drug will never be allowed to go onto the market.

And finally back to PMMA, the presence of which just redoubles the risks.  PMMA has similar effects to MDMA but is sower acting and more toxic. If the ecstasy tablet contains a significant proportion of PMMA (and some have been found to contain 25%) then the onset of the ‘high’ is delayed.  This might then lead to redosing and overdose.

So if anyone says their particular brand of ‘high grade’ ecstasy is safe, check their qualifications to see if they have any idea what they are talking about. MDMA is a dangerous drug and made all the more so by the inclusion of PMMA. You have been given the science and so now there’s no excuse.