Recreational Ecstasy User Dies, Responses Typical: How about publicizing the tox screens?

In a post on the death of Heath Ledger a year ago I talked about the frustration of not being able to review the toxicity panels from his body tissues after the autopsy. In the end, the medical examiner report just said something along the lines of “in my professional opinion it was the combination of drugs which did him in”. Which one might interpret as meaning the tox panels did not identify an apparently lethal level of any one particular drug (or its metabolites). But as an interested party, I would like to see the numbers. Because in my view they would reinforce the message. Whether it be a drug interaction or a loss of tolerance (or for that matter a tolerance issue) that is associated with a highly public drug toxicity case, it is an opportunity to help people to understand basic pharmacological concepts as they apply to recreational drug use. Another sad case is in the news this month and once again, the data would be exceptionally helpful.
An Australian woman died after allegedly taking two ecstasy tablets.

Neville and Gerry Bebendorf, both high school teachers, are left to mourn their eldest daughter, whom Mrs Bebendorf described as “a beautiful, fragile person who touched many hearts”.
“Rosie was cruelly treated by unscrupulous people who took advantage of her vulnerability and generosity,” she said.
“If any good is to come of this, it may serve as a warning to young people never to start taking drugs.”

To get the attitude out of the way—is the mom kidding us? A 28 year old woman taking a couple of Ecstasy tablets voluntarily is being “cruelly treated” and “taken advantage of”? Whatevs….
This is a tragedy and by no means the first. Additional coverage of this story notes:

Tony Wood, whose 15-year-old daughter Anna died after taking ecstasy for the first time in Sydney 13 years ago, said not enough was being done to address Australia’s “enormous” drug problem.
…
He said he was regularly contacted about deaths linked to ecstasy but few were ever made public.
“A year after Anna’s death, friends of ours lost their son. He had half a tablet at 4pm then the other half at 9pm. He was dead by 11pm. Police couldn’t believe such a big, strapping young man could be knocked down by a little pill.”

These reports keep trickling along, for those who are paying attention. It is absolutely not in question that people do die after consuming tablets that they and their friends/associates apparently thought were “Ecstasy”. One presumes in most cases that the individual thought “Ecstasy” was MDMA and MDMA alone. As in this little set of news reports, it is interesting that it is frequently emphasized that the individual in question took Ecstasy (or cocaine, see Len Bias) for the first time, although I suspect the validity of such claims is poor. Parents are usually clueless and teen associates sure aren’t going to be motivated to ‘fess up to having rolled with the decedent a dozen times in the past. It is also quite fascinating that the individuals are represented as having consumed a fairly low number of tablets. In this case two, meaning by most prior published reports somewhere between 100 to 300 mg of MDMA, assuming that was the content. Depending on content and how large the woman was probably 1.3 to 2 mg/kg at the low end and up to 6 mg/kg. This latter depends on about the high water mark for MDMA tablet content (150 mg) and a 50 kg (110 lb) woman.
Let us start with the reader comments on the courier mail piece. You will find the usual protestations about Alcohol and Aspirin or whathaveyou causing more deaths. And about how generally Evil are Alcohol and Tobacco and how great and Awesomest is Ecstasy.
e.g.:

Oh and FYI in recent studies ecstasy is actually ranked to be causing less harm then other legal drugs such as alcohol and tabacco.
At events I have been to everyone who has consumed ecstasy is in a pleasent state and enjoying themselves. Generally all of the trouble causers have been drinking alcohol and not taking drugs.

or:

Have you thought that some people decide on mdma because they feel it is actually safer then drinking. 1 – you have control of yourself. Your not vomiting. Your not killing you liver. Your not falling over. Your not getting in random fights. Your not making irrational choices. Your not getting fat with all the carbs. I could go on…. Many educated people take MDMA…. Not random e pills on the street but MDMA – do the research.

More interesting to me, and relevant to the leadoff about tox reports are the following:

I find it disturbing that the media makes it out that Ecstasy is the cause of the death… I gurantee you 100% that this so called estasy did not contain MDMA, which is what E is meant to have in it. In holland there is no death because you can test it.

and:

All of you that are saying E is just MDMA and nothing else – and that makes it safe. You are all WRONG! E is always cut with something just like speed. There could be ANYTHING in your pill.

there are more in a similar vein, but head on over to bluelight for additional comment such as:

Quote:
Originally Posted by FlowMotion View Post
Do they have any ideas what was in the pills? My guess is PMA.
I agree. No way can they od on two pure as can be MDMA pills unless they didn’t drink a drip of water a couple hours before popping and the whole experience.

or

It’s annoying how the media insinuate that the person has died from standard ecstasy without including the fact that it most likely wasn’t MDMA. If someone passes someone a piece of metal in the shape of a pill, says it’s ecstasy, and the person dies… will the media report it as an ecstasy overdose? YES! Argh! So angry!</small

and

I love how the media covers these stories. It’s always the same biased bullshit. All the coverage about this incident should read something like ‘woman trying to purchase MDMA is sold fake drugs and dies from REAL FUCKING REASON HERE. But of course that’s not going to happen. We need to blow blue moon stories like this out of proportion so specific drugs can continue being illegal.

Hopefully you get the flavor. They have a point. Street ecstasy tablets are notoriously variable in psychoactive drug content. Structurally related compounds such as MDA, MDE and good ol’ Methamphetamine are commonly detected. Behaviorally related but structurally unrelated caffeine is also observed, as are a host of what might be “filler” compounds such as tylenol. Paramethoxyamphetamine (PMA) is a decent suspect as it does seem to exhibit a fairly steep dose-response function. Another way to look at this is a narrow recreational-index, i.e. the difference between the dose which produces the desired recreational effect and adverse consequences in a substantial fraction of the population is small.
Nevertheless, it is also the case that MDMA itself is capable of producing the types of lethal and near-lethal effects that are reported in Case Reports and the popular media. There are the occasional reports in which no other suspect drugs are reported. Moreover, resort to the animal research literature shows that under certain conditions, MDMA and MDMA alone is capable of causing death in mice, rats, dogs and nonhuman primates. The best reference is Hardman et al. 1973 because this is an LD₅₀ study. If you keep close track of the literature (where endpoints other than death were the experimental goal) you will see the occasional (near) lethal condition or unusual outcome reported in studies but you may have to read the Methods carefully.
This latter type of evidence gives us to suggest that lethal consequences are dose related. Duh. However some of the human case reports include blood levels of MDMA that are pretty consistent with only one or two tablets consumed. Much like the assertions in the newscoverage linked above.
The thing is, we don’t really know. Did the case reported in the popular media take lots and lots of MDMA, more than was reported? Did s/he obtain “ecstasy” tablets that were actually PMA, Meth or some combination with MDMA? All of this is knowable and likely will eventually be known by the Medical Examiner (or whatever the Aussie version of that job is). Question is, will it be published? Will we get all the details?
We should. It is imperative that if this woman has died from MDMA and MDMA alone that the yammering commenters who just know that it “must have” been PMA are informed. Similarly, if it was PMA or METH or some combination or whateverelse that is not MDMA, we need to chalk that up on the board too.